ScienceWeek

SCIENCEWEEK

November 24, 2006

Vol. 10 - Number 46

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Between the fifth and tenth days the lump of stem cells differentiates into the overall building plan of the mouse embryo and its organs. It is a bit like a lump of iron turning into the space shuttle. In fact it is the profoundest wonder we can still imagine and accept, and at the same time so usual that we have to force ourselves to wonder about the wondrousness of this wonder.

-- Miroslav Holub

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Contents:

1. Anthropology: A New Analysis of Neanderthal Genomic DNA. Our knowledge of Neanderthals is based on a limited number of remains and artifacts from which we must make inferences about their biology, behavior, and relationship to ourselves. A new analysis of the Neanderthal genome advances our understanding of the evolutionary relationship of Homo sapiens and Homo neanderthalensis and signifies the dawn of Neanderthal genomics...

2. Computer Science: On the Mentation of Robots. Like us, robots need to constantly ascertain where they are in the world, and like us, they work better if they have an accurate sense of self. New work (1) shows that robots equipped with an algorithm that infers their own physical structure from stored sensory data -- dreams of their prior actions, so to speak --perform better in a simple forward locomotion...

3. Medicine: On Red Grapes and Health. New work reports that mice fed a diet akin to coconut cream pie for every meal showed a striking increase in survival and health when their chow was supplemented with resveratrol, a polyphenolic compound found in red grapes or wine. Compared with animals fed a more standard diet, mice fed the high-calorie (60% from fat) diet without resveratrol had a shorter lifespan...

4. Plant Biology: On the Plant Immune System. Plant pathogens use diverse life strategies. Pathogenic bacteria proliferate in intercellular spaces (the apoplast) after entering through gas or water pores (stomata and hydathodes, respectively), or gain access via wounds. Nematodes and aphids feed by inserting a stylet directly into a plant cell. Fungi can directly enter plant epidermal cells...


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Also Noted:

Why Pandas Do Handstands. And Other Curious Truths About Animals. Augustus Brown. Free Press (Simon and Schuster), New York, 2006. Hardback: 317 pp. $15.95, C$19.99. ISBN 1416531904. More information at: http://www.amazon.com/exec/obidos/ASIN/1416531904/scienceweek

The Theory of Almost Everything. The Standard Model, the Unsung Triumph of Modern Physics. Robert Oerter. Plume (Penguin Group USA), New York, 2006. Paperback: 333 pp., illus. $15, C$18.50. ISBN 0452287863. Reprint, 2005 ed. More information at: http://www.amazon.com/exec/obidos/ASIN/0452287863/scienceweek

Theories for Everything. An Illustrated History of Science from the Invention of Numbers to String Theory. John Langone, Bruce Stutz, and Andrea Gianopoulos. National Geographic Society, Washington, DC, 2006. Hardback: 408 pp., illus. $40, C$54. ISBN 0792239121. More information at: http://www.amazon.com/exec/obidos/ASIN/0792239121/scienceweek

Strange Curves, Counting Rabbits, and Other Mathematical Explorations. Keith Ball. Princeton University Press, Princeton, NJ, 2006. Paperback: 267 pp., illus. $18.95, £12.50. ISBN 0691127972. Reprint, 2003 ed. More information at: http://www.amazon.com/exec/obidos/ASIN/0691127972/scienceweek

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1. ANTHROPOLOGY: A NEW ANALYSIS OF NEANDERTHAL GENOMIC DNA

The following points are made by J.P. Noonan et al (Science 2006 314:1113)

1) Neanderthals are the closest hominid relatives of modern humans (1). As late as 30,000 years ago, humans and Neanderthals coexisted in Europe and western Asia (2). Since that time, our species has spread across Earth, far surpassing any previous hominid or primate species in numbers, technological development, and environmental impact, while Neanderthals have vanished. Molecular studies of Neanderthals have been exclusively constrained to the comparison of human and polymerase chain reaction (PCR)–amplified Neanderthal mitochondrial sequences, which suggest that the most recent common ancestor of humans and Neanderthals existed ~500,000 years ago, well before the emergence of modern humans (3–5).

2) Further analyses of mitochondrial data, including the comparison of mitochondrial sequences obtained from several Neanderthals and early modern humans, suggest little or no admixture between Neanderthal and modern human populations in Europe (3,4). However, a major limitation of all prior molecular studies of Neanderthals is that mitochondrial sequences reflect only maternal inheritance of a single locus. Accordingly, in the absence of Neanderthal autosomal and Y-chromosome sequences, the assessment of human-Neanderthal admixture remains incomplete. Mitochondrial data also provide no access to the gene and gene regulatory sequence differences between humans and Neanderthals that would help to reveal biological features unique to each. These insights await the recovery of Neanderthal genomic sequences.

3) The introduction of high-throughput sequencing technologies and recent advances in metagenomic analysis of complex DNA mixtures now provide a strategy to recover genomic sequences from ancient remains. In contrast to previous efforts to obtain ancient sequences by direct analysis of extracts (3–5), metagenomic libraries allow the immortalization of DNA isolated from precious ancient samples, obviating the need for repeated destructive extractions. In addition, once an ancient DNA fragment is cloned into a metagenomic library, it can be distinguished from contamination that might be introduced during subsequent PCR amplification or sequencing by the vector sequences linked to each library-derived insert.

4) In summary: Our knowledge of Neanderthals is based on a limited number of remains and artifacts from which we must make inferences about their biology, behavior, and relationship to ourselves. The authors describe the characterization of these extinct hominids from a new perspective, based on the development of a Neanderthal metagenomic library and its high-throughput sequencing and analysis. Several lines of evidence indicate that the 65,250 base pairs of hominid sequence so far identified in the library are of Neanderthal origin, the strongest being the ascertainment of sequence identities between Neanderthal and chimpanzee at sites where the human genomic sequence is different. These results enabled the authors to calculate the human-Neanderthal divergence time based on multiple randomly distributed autosomal loci. The analyses suggest that on average the Neanderthal genomic sequence obtained and the reference human genome sequence share a most recent common ancestor ~706,000 years ago, and that the human and Neanderthal ancestral populations split ~370,000 years ago, before the emergence of anatomically modern humans. The finding that the Neanderthal and human genomes are at least 99.5% identical led the authors to develop and successfully implement a targeted method for recovering specific ancient DNA sequences from metagenomic libraries. This initial analysis of the Neanderthal genome advances our understanding of the evolutionary relationship of Homo sapiens and Homo neanderthalensis and signifies the dawn of Neanderthal genomics.

References (abridged):

1. P. Mellars, Nature 432, 461 (2004).

2. F. H. Smith, E. Trinkaus, P. B. Pettitt, I. Karavanic, M. Paunovic, Proc. Natl. Acad. Sci. U.S.A. 96, 12281 (1999).

3. M. Krings et al., Cell 90, 19 (1997).[Medline]

4. M. Krings et al., Proc. Natl. Acad. Sci. U.S.A. 96, 5581 (1999).

5. S. Pääbo et al., Annu. Rev. Genet. 38, 645 (2004).

Science http://www.sciencemag.org

ScienceWeek http://scienceweek.com

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2. COMPUTER SCIENCE: ON THE MENTATION OF ROBOTS

The following points are made by Christoph Adami (Science 2006 314:1093)

1) Like us, robots need to constantly ascertain where they are in the world, and like us, they work better if they have an accurate sense of self. New work (1) shows that robots equipped with an algorithm that infers their own physical structure from stored sensory data -- dreams of their prior actions, so to speak --perform better in a simple forward locomotion task than robots whose decisions are not dream-inspired. Furthermore, robots that use these self-models to plan future actions can recover autonomously from injuries, by adapting their gait to compensate for the changed circumstances.

2) A robot's most formidable enemy is an uncertain and changing environment. Typically, robots depend on internal maps (either provided or learned), and sensory data to orient themselves with respect to that map and to update their location. If the environment is changing or noisy, the robot has to navigate under uncertainty, and constantly update the probabilities that a particular action will achieve a particular result. The situation becomes even worse if the robot's own shape and configuration can change, that is, if its internal model becomes inaccurate. In most cases, such an event constitutes the end of that particular robot's adventure.

3) Bongard et al (1) aim to improve a robot's robustness in an environment that may include damage to the robot. At the beginning of a self-modeling cycle, a four-legged robot without an internal model of itself performs actions (while on a flat surface), and records its own response via tilt sensors and angle sensors in its joints. The robot then computationally tests candidate self-models, by re-imagining the actions it just performed and comparing the behavior of the model with its memory of the results -- that is, the robot tries to explain the observed relationship between sensory data and leg actuation by making assumptions about its own configuration.

4) Even though the number of tested models is comparatively small (by only allowing a limited arrangement of limbs and their length), it is easy to imagine that many models can end up explaining the recorded behavior equally well (or equally badly). In the next stage of the cycle, the robot uses these equivalent models to find an action that would serve as the best way to discriminate among them. In other words, we could fancifully imagine the robot thinking: "Well, these three models all seem to work equally well with what I remember, but it seems to me that if I stick what I think is one of my legs out just so, then I can discover if I have a fourth leg or not." To narrow the choice of models, the robot then proceeds to test the action that provides the most information about the model's identity in the real world, and the cycle begins again. After 16 such cycles, the robot tests the accuracy of the final self-model by performing a set of actions that, according to this model, will result in the largest linear distance traveled, and then executing these actions. The total distance traveled can then be used as a measure of the accuracy of the robot's model of itself.(2-4)

References:

1. J. Bongard, V. Zykov, H. Lipson, Science 314, 1118 (2006).

2. T. M. Cover, J. A. Thomas, Elements of Information Theory (Willey, New York, 1991).

3. S. Thrun, W. Burgard, D. Fox, Probabilistic Robotics (MIT Press, Cambridge, MA, 2005).

4. C. Koch, The Quest for Consciousness (Roberts, Greenwood Village, CO, 2004).

Science http://www.sciencemag.org

ScienceWeek http://scienceweek.com

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3. MEDICINE: ON RED GRAPES AND HEALTH

The following points are made by M. Kaeberlein and P.S. Rabinovitch (Nature 2006 444:280):

1) New work (1) reports that mice fed a diet akin to coconut cream pie for every meal showed a striking increase in survival and health when their chow was supplemented with resveratrol, a polyphenolic compound found in red grapes or wine. Compared with animals fed a more standard diet, mice fed the high-calorie (60% from fat) diet without resveratrol had a shorter lifespan. They also showed many of the problems that plague humans who overindulge at the dinner table, including obesity, insulin resistance and heart disease. Baur et al (1) found that although resveratrol did not prevent obesity, it did prevent obesity-associated disease, at least in one strain of mouse, and conferred a nearly normal lifespan on these mice.

2) With the present epidemic of obesity in some Western societies, this could be very good news. But might resveratrol improve health or lifespan beyond that achieved with a healthy diet? The link between diet and longevity has been known to gerontologists since the discovery in the 1930s that reduced caloric intake can increase the lifespan of rodents by up to 50%. Dietary restriction has since been observed to have a similar effect on longevity in many different organisms, including yeast, worms, flies, spiders and fish. Importantly, dietary restriction not only increases lifespan, but it also delays the onset of nearly all age-associated diseases. For this reason, most gerontologists believe that dietary restriction affects the intrinsic ageing process at a fundamental level. The genetic pathways influencing this phenomenon are currently a hot topic of research and debate.

3) Like dietary restriction, resveratrol has long been known to have interesting properties. During the 1990s it was extensively studied as a potential link between improvements in a variety of health indicators and moderate consumption of red wine (2). The antioxidant properties of resveratrol, in particular, have been suggested to account for many of its beneficial properties, including putative cardio-protective and anticancer activities, as well as providing protection against liver failure. Here it is noteworthy that Baur et al (1) show that resveratrol has a profound ability to prevent liver damage associated with the high-fat diet.

4) Resveratrol became of particular interest to gerontologists with the report (3) that it can increase lifespan in yeast by activating particular enzymes (protein deacetylases) of the Sir2 family of proteins (sirtuins). Sirtuins are evolutionarily conserved mediators of longevity that might also play a role in lifespan extension through dietary restriction (4). Although the results from the initial study of resveratrol in yeast remain controversial (5), subsequent work has suggested that resveratrol has modest effects on lifespan in both worms and flies, and a more substantial effect on lifespan in a short-lived fish. Based on these findings, it has been proposed that resveratrol increases lifespan in several different organisms by a mechanism similar to dietary restriction. Baur et al (1) favour the view that many (perhaps all) of the beneficial properties of resveratrol are the result of increased sirtuin activity, and various studies have supported the idea that sirtuins underlie the effects attributed to resveratrol in vivo. However, there is a lack of biochemical evidence that resveratrol directly increases sirtuin-mediated deacetylation of biologically relevant substrates, and some evidence that it may not (5).

References (abridged):

1. Baur, J. A. et al. Nature 444, 337-342 (2006).

2. Soleas, G. J., Diamandis, E. P. & Goldberg, D. M. Clin. Biochem. 30, 91-113 (1997).

3. Howitz, K. T. et al. Nature 425, 191-196 (2003).

4. Longo, V. D. & Kennedy, B. K. Cell 126, 257-268 (2006).

5. Kaeberlein, M. et al. J. Biol. Chem. 280, 17038-17045 (2005).

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

ScienceWeek http://scienceweek.com

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4. PLANT BIOLOGY: ON THE PLANT IMMUNE SYSTEM

The following points are made by J.D. Jones and J.L. Dangl (Nature 2006 444:323):

1) Plant pathogens use diverse life strategies. Pathogenic bacteria proliferate in intercellular spaces (the apoplast) after entering through gas or water pores (stomata and hydathodes, respectively), or gain access via wounds. Nematodes and aphids feed by inserting a stylet directly into a plant cell. Fungi can directly enter plant epidermal cells, or extend hyphae on top of, between, or through plant cells. Pathogenic and symbiotic fungi and oomycetes can invaginate feeding structures (haustoria) into the host cell plasma membrane. Haustorial plasma membranes, the extracellular matrix, and host plasma membranes form an intimate interface at which the outcome of the interaction is determined. These diverse pathogen classes all deliver effector molecules (virulence factors) into the plant cell to enhance microbial fitness.

2) Plants, unlike mammals, lack mobile defender cells and a somatic adaptive immune system. Instead, they rely on the innate immunity of each cell and on systemic signals emanating from infection sites (1-3). The authors previously reviewed disease resistance (R) protein diversity, polymorphism at R loci in wild plants and lack thereof in crops, and the suite of cellular responses that follow R protein activation (1). The authors hypothesized that many plant R proteins might be activated indirectly by pathogen-encoded effectors, and not by direct recognition. This "guard hypothesis" implies that R proteins indirectly recognize pathogen effectors by monitoring the integrity of host cellular targets of effector action (1,4). The concept that R proteins recognize "pathogen-induced modified self" is similar to the recognition of "modified self" in "danger signal" models of the mammalian immune system (5).

3) It is now clear that there are, in essence, two branches of the plant immune system. One uses transmembrane pattern recognition receptors (PRRs) that respond to slowly evolving microbial- or pathogen-associated molecular patterns (MAMPS or PAMPs), such as flagellin. The second acts largely inside the cell, using the polymorphic NB-LRR protein products encoded by most R genes (1). They are named after their characteristic nucleotide binding (NB) and leucine rich repeat (LRR) domains. NB-LRR proteins are broadly related to animal CATERPILLER/NOD/NLR proteins and STAND ATPases. Pathogen effectors from diverse kingdoms are recognized by NB-LRR proteins, and activate similar defense responses. NB-LRR-mediated disease resistance is effective against pathogens that can grow only on living host tissue (obligate biotrophs), or hemi-biotrophic pathogens, but not against pathogens that kill host tissue during colonization (necrotrophs).

4) In summary: Many plant-associated microbes are pathogens that impair plant growth and reproduction. Plants respond to infection using a two-branched innate immune system. The first branch recognizes and responds to molecules common to many classes of microbes, including non-pathogens. The second branch responds to pathogen virulence factors, either directly or through their effects on host targets. These plant immune systems, and the pathogen molecules to which they respond, provide extraordinary insights into molecular recognition, cell biology, and evolution across biological kingdoms. A detailed understanding of plant immune function will underpin crop improvement for food, fiber, and biofuels production.

References (abridged):

1. Dangl, J. L. & Jones, J. D. G. Plant pathogens and integrated defence responses to infection. Nature 411, 826-833 (2001)

2. Ausubel, F. M. Are innate immune signaling pathways in plants and animals conserved?. Nature Immunol. 6, 973-979 (2005)

3. Chisholm, S. T., Coaker, G., Day, B. & Staskawicz, B. J. Host-microbe interactions: shaping the evolution of the plant immune response. Cell 124, 803-814 (2006)

4. van der Biezen, E. A. & Jones, J. D. G. Plant disease resistance proteins and the gene-for-gene concept. Trends Biochem. Sci. 23, 454-456 (1998)

5. Matzinger, P. The danger model: a renewed sense of self. Science 296, 301-305 (2002)

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

ScienceWeek http://scienceweek.com

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