ScienceWeek

SCIENCEWEEK

September 22, 2006

Vol. 10 - Number 38

-------------------------------

Back issues of ScienceWeek can be searched for subjects, names, terms, etc. at: http://scienceweek.com/swfr.htm

--------------------------------

There are living systems, there is no "living matter".

-- Jacques Lucien Monod (1910-1976)

--------------------------------

Contents (full reports below):

1. Cell Biology: On Tissue Response to Injury. Animals have remarkable abilities to respond to injuries. Within 1 week after the surgical removal of 70% of a rodent's liver, the organ can regenerate its original mass and function normally. The remaining cells of an injured liver need to obtain enough energy and building materials to support rapid cell division and tissue regrowth. This process...

2. Chemistry: On the Organic Approach to Asymmetric Catalysis. When chemists make chiral compounds -- molecules that behave like object and mirror image, such as amino acids, sugars, drugs, or nucleic acids -- they like to use asymmetric catalysis, in which a chiral catalyst selectively accelerates the reaction that leads to one mirror-image isomer, also called enantiomer. For example, the "Monsanto process" uses...

3. Evolutionary Biology: On Human Brain Size and the Genome. The human brain is supposed to set us apart from other animals. If so, our genome must retain the imprint of our brain's recent evolution. So which parts of our genome have seen the most change, and are these genomic innovations linked directly to our unique brain structure and function? New work describes how researchers have clocked the speed at which...

4. Astronomy: On the First Galaxies. Determining when the first stars and galaxies formed is a matter of profound importance: fueled by primordial hydrogen, these bodies triggered the nucleosynthesis of the heavier elements, such as carbon, nitrogen and oxygen, that are the basis of life. By studying the first galaxies, we can also hope to understand how the Universe formed and...

--------------------------------

Also Noted:

Space-Time, Relativity, and Cosmology. Jose Wudka. Cambridge University Press, Cambridge, 2006. Hardback: 330 pp., illus. $55. ISBN 0521822807. More information at: http://www.amazon.com/exec/obidos/ASIN/0521822807/scienceweek

From Cosmos to Chaos. The Science of Unpredictability. Peter Coles. Oxford University Press, Oxford, 2006. Hardback: 224 pp., illus. £25. ISBN 0198567626. More information at: http://www.amazon.com/exec/obidos/ASIN/0198567626/scienceweek

Distilling Knowledge. Alchemy, Chemistry, and the Scientific Revolution. Bruce T. Moran. Harvard University Press, Cambridge, MA, 2006. Paperback: 220 pp., illus. $16.95. ISBN 0674022491. More information at: http://www.amazon.com/exec/obidos/ASIN/0674022491/scienceweek

The Cosmic Century. A History of Astrophysics and Cosmology. Malcolm S. Longair. Cambridge University Press, Cambridge, 2006. Hardback: 561 pp., illus. $60. ISBN 0521474361. More information at: http://www.amazon.com/exec/obidos/ASIN/0521474361/scienceweek

Special Note: A New Book by the Editor of ScienceWeek:

Junk Science. How Politicians, Corporations, and Other Hucksters Betray Us. Dan Agin. Thomas Dunne Books/St. Martin's Press, New York, 2006. Hardback: 336 pp., $24.95. ISBN 0312352417. Publication date: October 3, 2006. More information at: http://www.amazon.com/exec/obidos/ASIN/0312352417/scienceweek

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

1. CELL BIOLOGY: ON TISSUE RESPONSE TO INJURY

The following points are made by Dawn L. Brasaemle (Science 2006 313:1581):

1) Animals have remarkable abilities to respond to injuries. Within 1 week after the surgical removal of 70% of a rodent's liver, the organ can regenerate its original mass and function normally. The remaining cells of an injured liver need to obtain enough energy and building materials to support rapid cell division and tissue regrowth. This process depends on the cell's ability to metabolize fatty acids that are released from adipose tissue. New work (1) reports that a common cellular protein plays a critical role in the liver's metabolic push to proliferate and regenerate.

2) An injured liver produces cytokine signals that trigger the release of fatty acids from adipose tissue into circulation. These fatty acids are taken up by hepatocytes where they are esterified and stored as triacylglycerols in large lipid droplets before ultimately being metabolized (2). Fernández et al (1) show that mice genetically altered to lack the protein caveolin-1 had impaired liver regeneration (after a partial hepatectomy) and reduced survival under normal diet conditions. Residual hepatocytes failed to accumulate large lipid droplets and cell division stalled, leading to the death of most animals within 72 hours. By contrast, when caveolin-1 null mice were fed large amounts of dietary glucose before and after hepatectomy, the animals displayed nearly normal liver regeneration and survival.

3) Caveolins have been extensively characterized as major protein components of caveolae, flask-shaped invaginations of animal cell plasma membranes. Caveolin-1 and -2 are expressed in most cell types, whereas caveolin-3 is expressed primarily in cardiac, skeletal, and smooth muscle (3). Several functions have been ascribed to caveolins, including maintenance of caveolar structure, mediation of endocytosis and transcytosis of molecules attached to the cell surface, organization of signaling proteins, and less well understood roles in cellular cholesterol homeostasis and fatty acid transport.

4) How does caveolin-1 regulate lipid metabolism in hepatocytes? Fatty acids likely transit across the hepatocyte plasma membrane both by simple diffusion and with the assistance of putative membrane-associated fatty acid transporters, one of which is caveolin-1. Another putative fatty acid transporter, CD36/FAT, also localizes to caveolae (4). Furthermore, the disruption of caveolae by depleting membrane cholesterol or by inhibiting caveolin expression or function reduces the uptake of fatty acids into cells (4) Conversely, over-expression of caveolin-1 increases the cholesterol content of the plasma membrane and fatty acid uptake into cultured cells (5), although it is not clear whether caveolin-1 is directly involved in fatty acid transport in this case. The precise molecular mechanisms of fatty acid uptake remain controversial. However, it is generally accepted that net uptake is coupled to intracellular metabolism of fatty acids.

References (abridged):

1. M. A. Fernández et al., Science 313, 1628 (2006)

2. G. C. Farrell, Hepatology 40, 1252 (2004)

3. A. W. Cohen et al., Physiol. Rev. 84, 1341 (2004)

4. R. Ehehalt et al., Mol. Cell. Biochem. 284, 135 (2006)

5. T. Meshulam et al., Biochemistry 45, 2882 (2006)

Science http://www.sciencemag.org

ScienceWeek http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

2. CHEMISTRY: ON THE ORGANIC APPROACH TO ASYMMETRIC CATALYSIS

The following points are made by B. List and J. W. Yang (Science 2006 313:1584):

1) When chemists make chiral compounds -- molecules that behave like object and mirror image, such as amino acids, sugars, drugs, or nucleic acids -- they like to use asymmetric catalysis, in which a chiral catalyst selectively accelerates the reaction that leads to one mirror-image isomer, also called enantiomer. For example, the "Monsanto process" uses a chiral rhodium catalyst to synthesize the drug L-dopa, used to treat Parkinson's disease (1).

2) For decades, the generally accepted view has been that there are two classes of efficient asymmetric catalysts: enzymes and synthetic metal complexes (2). However, this view is currently being challenged, with purely organic catalysts emerging as a third class of powerful asymmetric catalysts. Most biological molecules are chiral and are synthesized in living cells by enzymes using asymmetric catalysis. Chemists also use enzymes or even whole cells to synthesize chiral compounds. Such biological catalysis is increasingly used on an industrial scale and is particularly preferred in hydrolytic reactions. The other class of accepted and efficient chiral catalysts, metal complexes, are reagents based on inorganic chemistry. Transition metal catalysts are particularly useful for asymmetric hydrogenations, but may leave possibly toxic traces of heavy metals in the product.

3) In contrast, in organocatalysis, a purely organic and metal-free small molecule is used to catalyze a chemical reaction. In addition to enriching chemistry with another useful strategy for catalysis, this approach has some important advantages. Small organic molecule catalysts are generally stable and fairly easy to design and synthesize. They are often based on nontoxic compounds, such as sugars, peptides, or even amino acids, and can easily be linked to a solid support, making them useful for industrial applications. However, the property of organocatalysts most attractive to organic chemists may be the simple fact that they are organic molecules.

4) Organocatalysts have been used sporadically throughout the last century; indeed, an organic catalyst was used in one of the very first examples of a nonenzymatic asymmetric catalytic reaction (3). But recently, this area has grown at a breathtaking pace. Within a few years, powerful organocatalysts for a wide range of reactions have been designed and developed (4,5). A particularly appealing discovery of great potential is the use of chiral Brønsted acids as organocatalysts. Organic Brønsted acids function by donating a proton to the substrate. They have been used as catalysts for a variety of reactions since the beginnings of modern chemistry, but applications in asymmetric catalysis have been extremely rare. A breakthrough in this area came when researchers developed highly active Brønsted acid organocatalysts that incorporate a urea motif as the active principle.

References (abridged):

1. W. S. Knowles, Adv. Synth. Cat. 345, 3 (2003)

2. K. C. Nicolaou, E. J. Sorensen, Classics in Total Synthesis (Wiley-VCH, Weinheim, 1996), p. 344

3. G. Bredig, P. S. Fiske, Biochem. Z. 46, 7 (1912)

4. A. Berkessel, H. Gröger, Asymmetric Organocatalysis (VCH, Weinheim, Germany, 2005)

5. A. B. Northrup, D. W. C. MacMillan, Science 305, [1752] (2004)

Science http://www.sciencemag.org

ScienceWeek http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

3. EVOLUTIONARY BIOLOGY: ON HUMAN BRAIN SIZE AND THE GENOME

The following points are made by C.P. Ponting and G. Lunter (Nature 2006 443:149):

1) The human brain is supposed to set us apart from other animals. If so, our genome must retain the imprint of our brain's recent evolution. So which parts of our genome have seen the most change, and are these genomic innovations linked directly to our unique brain structure and function? New work (1) describes how researchers have clocked the speed at which various human genome regions have changed in recent times. The clear winner of this race is human accelerated region 1 (HAR1), part of an RNA gene whose pattern of expression is suitably poised to influence the migration of neurons in the developing cortex. The authors' second and equally important finding is that all but two of the most-accelerated regions lie outside protein-coding sequences --in the enigmatic "dark matter" of the human genome.

2) Time and again, humans' sense of cognitive superiority over other primates has failed to find a solid foundation in structural variations of the brain. The brains of humans and chimpanzees are anatomically not so different (2), except in scale. About two million years ago, the hominin brain began to enlarge until, in modern times, it has become about three times larger than that of chimpanzees. Size matters, but it is equally likely that alterations in cellular structures contribute to the cognitive differences between the two species. All these changes must have left their impression on the human genome. Yet evidence directly linking DNA differences to anatomical or behavioral differences between these two species has been, at best, fragmentary (3).

3) Geneticists have long labored under the assumption that it is the DNA sequences that code for proteins that must have borne the brunt of adaptive change (3). This notion has continued despite the scarcity of coding differences between chimpanzees and humans (4), and the recent appreciation that a greater proportion of apparently functional DNA sequence lies outside protein-coding sequence than inside (5). What was needed, instead, was an unbiased genome-wide scan to pinpoint the few regions -- of whatever type -- where the DNA has remained essentially static over tens and hundreds of million years in diverse species, yet which, in the past few million years of human evolution, have altered especially rapidly.

4) Such is Pollard and colleagues' computational scan of the human genome (1). Their study reveals a set of 49 regions (HAR1-HAR49), each with a sequence that is highly evolutionarily conserved among many mammals, but that has diverged rapidly in humans since our last common ancestor with chimpanzees. The fastest among them, HAR1, has accrued 18 changes in sequence in this time, when only one or no substitutions would be expected to occur by chance. How might these extraordinary changes be linked to the human brain's increased cognitive capabilities? The first clue came from the finding that HAR1F, one of two RNA genes containing HAR1, is expressed in the developing neocortex in the brains of humans and in those of another primate, the crab-eating macaque. This is intriguing, as the neocortex is most often associated with higher cognitive functions. Specifically, HAR1F is expressed in human Cajal-Retzius cells, for which a crucial role in redirecting migrating neurons has long been suspected. HAR1 thus emerges as a strong candidate for a determinant of innovative function in the human neocortex.

References (abridged):

1. Pollard, K. S. et al. Nature doi:10.1038/nature05113 (2006)

2. Semendeferi, K. , Lu, A. , Schenker, N. & Damasio, H. Nature Neurosci. 5, 272-276 (2002)

3. Hill, R. S. & Walsh, C. A. Nature 437, 64-67 (2005)

4. King, M. C. & Wilson, A. C. Science 188, 107-116 (1975)

5. Waterston, R. H. et al. Nature 420, 520-562 (2002)

Nature http://www.nature.com/nature

ScienceWeek http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

4. ASTRONOMY: ON THE FIRST GALAXIES

The following points are made by Richard McMahon (Nature 2006 443:151):

1) Determining when the first stars and galaxies formed is a matter of profound importance: fueled by primordial hydrogen, these bodies triggered the nucleosynthesis of the heavier elements, such as carbon, nitrogen and oxygen, that are the basis of life. By studying the first galaxies, we can also hope to understand how the Universe formed and evolved, and detect the younger progenitors of galaxies like our own Milky Way. New work (1) reports the discovery of the most distant galaxy yet, one whose photons must have left it 12.7 billion years ago, when the Universe was just 750 million years old, and some 8 billion years before the Sun and Earth were formed. And Bouwens and Illingworth (2) report on their search for galaxies even farther away, more than 13 billion light years from Earth.

2) The study of the most distant galaxies has much in common with archaeology: the farther back one looks, the scantier the evidence becomes, and the harder it is to draw conclusions. Two factors are responsible. First, there are the immense distances of around 10^(24) km implied by light journey times of more than 10 billion years; the brightness of a source diminishes with the inverse square of its distance. Second, there is the expansion of the Universe, which stretches the wavelength of light from distant objects by a factor 1+z. The quantity z is known as the redshift, as the expansion moves all observed wavelengths towards longer, redder wavelengths. The older an object is, the greater its redshift; but unfortunately, the redder one gets, the brighter the night sky becomes. As a result, searching for the very earliest objects becomes -- from the ground, at least --increasingly difficult.

3) Like archaeology, astronomy also has its Dark Ages from which evidence is particularly sparse. As the Universe expanded and cooled, neutral hydrogen and helium were created from the hot plasma of matter at the so-called "epoch of recombination", around 400,000 years after the Big Bang. As very few atoms remained ionized in this neutral Universe, very little radiation can be detected from this era. The situation changed only when the first generation of luminous sources -- massive stars, galaxies and accreting black holes -- reionized and "lit up" the gas in the Universe.

4) In recent years, the search for galaxies has been pushed back progressively towards these trailblazers. Improvements in solid-state detector technology have followed Moore's law, with a doubling of chip density every two years or so; mega-pixel devices and highly efficient, large-format red-sensitive detectors have arrived on wide-field imaging instruments, on a new generation of 8-meter-aperture telescopes, and on the refurbished Hubble Space Telescope (HST). From a redshift of 4.55 in 1996 (3), the earliest star-forming galaxy had been put back to z=6.56 by 2002 (4).

5) Iye et al (1), in their discovery, take us farther back to z=6.96. But the authors note that by comparison with observations at smaller redshifts, they would have expected to find around five galaxies in a survey of their scale. Bouwens and Illingworth (2) recount a similar story at redshifts of 7-8. Where they might by extrapolation have expected to find around ten galaxies, they found only one unconfirmed candidate. So could we now really be looking back to the very earliest phase of galaxy formation at the epoch of reionization? With the current results it is still hard to tell.(5)

References (abridged):

1. Iye, M. et al. Nature 443, 186-188 (2006)

2. Bouwens, R. J. & Illingworth, G. D. Nature 443, 189-192 (2006)

3. Hu, E. M. & McMahon, R. G. Nature 382, 231-233 (1996)

4. Hu, E. M. et al. Astrophys. J. 568, L75-L79 (2002)

5. Horton, A. et al. Proc. SPIE 5492, 1022-1032 (2004)

Nature http://www.nature.com/nature

ScienceWeek http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=