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ScienceWeek

SCIENCEWEEK

August 4, 2007

Vol. 11 - Number 30

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There is no place for dogma in science. The scientist is free to ask any question, to doubt any assertion, to seek any evidence, to correct any error.

-- J. Robert Oppenheimer (1904-1967)

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Contents (full text below):

1. Astronomy: Seeing Through Dark Matter

2. Anne McLaren (1927-2007)

3. Astronomy: Where Are the Invisible Galaxies?

4. Archaeology: Ancient Writing or Modern Fakery?

5. Neurology: An Awakening

6. Microbiology: The Inside Story

7. Genomic Biology: The Epigenomic Era Opens

8. Biodiversity: Climate Change and the Ecologist

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1.

Science 3 August 2007: Vol. 317. no. 5838, pp. 607 - 608 DOI: 10.1126/science.1144534

Astronomy: Seeing Through Dark Matter

Stacy McGaugh

The universe appears to be dominated by invisible components that astronomers call dark matter and dark energy. The astronomical evidence implicating dark matter has been apparent for a generation (1): The rotational speeds of objects in extragalactic systems exceed what can be explained by the visible mass of stars and gas. This discrepancy has led to the inference that there is more mass than meets the eye. However, this inference requires that Newton's law of gravitational force be extrapolated well beyond where it was established. In addition, laboratory searches for dark matter have yet to bear fruit. This lack of corroboration, combined with the increasing complexity and "preposterous" nature of a once simple and elegant cosmology, leads one to wonder if perhaps instead gravity is to blame.

Simply changing the force law on some large length scale does not work (2). One idea that has proven surprisingly resilient is the modified Newtonian dynamics (MOND) hypothesized by Milgrom (3) in 1983. Rather than change the force law at some large length scale, MOND subtly alters it at a tiny acceleration scale, around 10-10 m s-2. In systems with gravitational accelerations above this scale (e.g., Earth, the solar system), everything behaves in a Newtonian sense. It is only when accelerations become tiny, as in the outskirts of galaxies, that the modification becomes apparent.

MOND has successfully described the rotation curves of spiral galaxies (see the figure) (4). In case after case, MOND correctly maps the observed mass to the observed dynamics. Why would such a direct mapping exist between visible and total mass if in fact dark matter dominates? Moreover, MOND's explicit predictions for low surface brightness galaxies have been realized (5). In contrast, the dark matter paradigm makes less precise predictions (6) for rotation curves that persistently disagree with the data (7).

One problem is that researchers have found it difficult to create a version of MOND that satisfies the well-established tests of Einstein's general theory of relativity. This hurdle has now been overcome by Bekenstein (8). Testing Bekenstein's approach is in the early stages, but initial results look promising (9)

Despite the observational and theoretical successes, the picture for MOND is not all rosy. Many observations purport to falsify MOND, although often the evidence is less compelling than might be hoped. Perhaps the most serious observational challenge is from rich clusters of galaxies. These systems exhibit clear mass discrepancies that MOND fails to completely rectify (10). Even after application of the MOND formula, one still infers that there is as much unseen mass in these clusters as can be seen in stars and gas. Consequently, MOND appears to require dark matter itself--a considerable embarrassment for a theory that seeks to supplant the need for invisible mass.

It is tempting to conclude that this is the real dark matter, some fundamentally new type of particle outside the highly successful standard model of particle physics. However, it might just be the result of another missing mass problem in extragalactic astronomy: the missing baryon problem. Our inventory of ordinary matter (baryons)--the stars and gas that we can see directly--falls well short of the amount we expect from big bang nucleosynthesis (11). Perhaps the unseen mass required in clusters by MOND is merely these dark baryons. Indeed, this has happened before. For a long time, astronomers thought that most of the ordinary mass in clusters was visible stars. Only relatively recently have we come to appreciate that all the stars in all the cluster galaxies are outweighed by a hot, diffuse gas between them. Still more baryonic mass may await discovery there.

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2.

Science 3 August 2007: Vol. 317. no. 5838, p. 609 DOI: 10.1126/science.1147801

Anne McLaren (1927-2007)

Janet Rossant and Brigid Hogan

The death of Anne McLaren in England on 7 July 2007 has robbed us of a major leader in mammalian developmental biology and genetics. Not only was Anne a pioneer, she remained an active scientist whose influence extended across many other fields. Notably, she was a preeminent international figure in public policy debates around issues of reproductive technologies and stem cell research.

Anne's scientific career spanned more than 50 years, from early studies on embryo transfer to her most recent work on germ cell development. After receiving a D.Phil. in 1952 from Oxford University, she began her career at University College London, where she perfected techniques of embryo transfer in mice and demonstrated maternal uterine effects on embryonic patterning. This work was performed with her then-husband, Donald Michie, with whom she remained friends after they divorced in 1959. Sadly, he was with her in the car accident that took both their lives. With John Biggers, she showed for the first time that preimplantation mouse embryos cultured in a dish for 2 days could be returned to the mother's uterus to complete normal pregnancy. This combination of embryo culture and transfer enabled the development of human in vitro fertilization technologies. The media hype over the birth of these "brave new mice" in 1958 also gave Anne her first taste of public controversy around new reproductive technologies.

In 1959, Anne moved to Edinburgh to set up her own lab at the Institute of Animal Genetics, established by C. H. Waddington. There, she initiated research on a broad range of topics, including embryo implantation and chimera development. She describes this period of her long career as her favorite, when genetics, epigenetics (as defined by Waddington), reproductive biology, and developmental biology were coming together to define new ways of understanding mammalian embryonic development. Her classic monograph "Mammalian Chimaeras," published in 1976, gives an amazingly current view of the power of mouse chimeras to explore a variety of biological questions.

Anne moved back to London in 1974 to direct the Medical Research Council Mammalian Development Unit. Under her guidance, this became one of the world's preeminent centers for mammalian embryology and genetics. Many leading scientists developed their careers there, and many more, including us, were fortunate to receive Anne's mentorship. She was always ready to welcome visitors, give advice, and discuss scientific matters. You were subjected to tough questioning, but in a way that led to more rigorous experiments and deeper insight. As many will testify, Anne was also extremely supportive of scientists struggling to work outside the mainstream or with few resources. Her own research during this time turned to germ cell development and sex determination. With Elizabeth Simpson in the 1980s, she showed that the mouse gene encoding the male antigen H-Y was not related to the sex-determination gene on the Y chromosome. This began a chase that led to the cloning, by the Goodfellow and Lovell-Badge labs, of the true sex-determination gene, Sry, in 1990. She also showed the first location of germ cells in the embryo, and her work inspired the derivation of embryonic germ cell lines.

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3.

Science 3 August 2007: Vol. 317. no. 5838, pp. 594 - 595 DOI: 10.1126/science.317.5838.594

Astronomy: Where Are the Invisible Galaxies?

Adrian Cho

CARDIFF, UNITED KINGDOM -- Whorls of innumerable stars, galaxies shine across the boundless darkness, their ancient light recording the nature and history of the universe. So entwined are the notions of star, light, and galaxy that one might expect astronomers and astrophysicists to snicker at the seemingly absurd idea of a dark galaxy, one devoid of light and stars. But many say that such things must abound, and 92 researchers gathered here recently to hash out both how to detect them and whether the fact that they haven't seen any poses a serious challenge to some fundamental theories.*

The questions have been foisted upon astronomers by cosmologists and their understanding of how the universe blossomed from the big bang. According to the increasingly refined theory, 85% of the matter in the universe is not the ordinary matter that makes up stars and galaxies, planets and people. Rather, it is elusive dark matter that so far has revealed itself only through its gravity. As the infant universe grew, the dark matter condensed into enormous filaments and clumps, or "halos." These weighty objects pulled in hydrogen gas, which formed stars and galaxies.

But there's a catch: Simulations show that dark matter should have formed myriad clumps between 1/1000 and 1/1,000,000 as massive as the Milky Way galaxy. At first blush, these small halos should have accumulated gas and lit up as small "dwarf galaxies," thousands of which should whiz around the Milky Way. So far, astronomers have spotted only a few dozen nearby--although they're finding more. Various factors may have kept the small halos dark. But then space ought to teem with tiny dark galaxies, and astronomers have yet to find any. "If they don't exist, then it's an enormous problem for astrophysics," says Jonathan Davies, an astronomer at Cardiff University in the U.K.

But other astronomers say the so-called missing satellites problem is an artifact of the simulations, which do not account for how individual galaxies form. Instead, the simulations track the evolution of dark matter alone and then "paint" the galaxies onto filaments and clumps. "It could simply be that the assumptions that go into the [computer] code are wrong, and that if you do dark-matter-only simulations you get the wrong answers," says Albert Bosma of the Marseille Observatory in France.

Complicating matters, researchers do not agree on precisely what a dark galaxy is. Polite disagreement escalates to acrimony when discussion turns to the question of whether one group has actually spotted one.

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4.

Science 3 August 2007: Vol. 317. no. 5838, pp. 588 - 589 DOI: 10.1126/science.317.5838.588

Archaeology: Ancient Writing or Modern Fakery?

Andrew Lawler

RAVENNA, ITALY -- They look like a child's exercise in geometry. But the images Yousef Madjidzadeh projected onto a screen last month in a sweltering lecture hall elicited gasps from archaeologists. The symbols on three baked mud tablets display a hitherto unknown writing system and likely are part of a larger archive, claimed Madjidzadeh, chief of excavations near Jiroft in southeastern Iran. He believes that these inscriptions were made between 2200 and 2100 B.C.E. and could hold the key to understanding a sophisticated urban culture in Middle Asia.

The discovery of an ancient script is a momentous find. But the circumstances surrounding the excavation have raised doubts about the tablets' authenticity. "Everyone is convinced they are fake, but no one dares say it," whispered one archaeologist after the presentation. Such criticism galls Madjidzadeh and his supporters, who say that although one tablet was found by a villager, the other two are from a carefully excavated trench. "People are skeptical because these are so different. It is hard to accept something so completely new," says Massimo Vidale, a University of Bologna archaeologist who was present during the excavation.

The first writing -- cuneiform -- evolved over millennia in Mesopotamia and coalesced into a coherent system by 3200 B.C.E. in the southern Iraqi city of Uruk. Not long after, another script appeared on the western edge of Mesopotamia. Dubbed proto-Elamite, after the kingdom of Elam that later flourished beside Mesopotamia, the system resembles cuneiform, although its origin and meaning are a puzzle. Centuries later, toward the end of the 3rd millennium B.C.E., another set of symbols arose on the Iranian plateau: linear Elamite. Only a handful of examples exist, mainly from the Elam capital of Susa and mainly in the form of stone carvings paired with cuneiform. Some scholars doubt it is a coherent script; they believe it is an attempt by Elamite kings to appear as modern as their Mesopotamian neighbors.

Given the dearth of linear Elamite inscriptions, the Jiroft finds are attracting scrutiny. In early 2005, Madjidzadeh's team found a brick in the gateway of the main Jiroft mound. Dated to between 2480 and 2280 B.C.E., the brick is inscribed with signs that may be related to linear Elamite, Madjidzadeh says. Later that field season, a worker showed the dig director a tablet with odd symbols that he said came from a hole he dug a half-kilometer from the mound.

Returning last year, Madjidzadeh had a student dig a trench at the spot. The team promptly recovered a second tablet. The next day, Madjidzadeh came to oversee the work; he uncovered the third tablet. The three tablets appear to show a progression. One has eight simple geometric signs, another has 15 slightly more complex signs, and the third has 59 signs of an even more complex nature, all inscribed in wet clay. On the back of each, apparently scratched into the mud brick after it was dry, are inscriptions that may be related to linear Elamite. Madjidzadeh believes he has stumbled on an archive, and that a librarian-scribe made the marks on the back of each tablet. He believes the tablets reveal linear Elamite's evolution from simple geometrical system to final complex form.

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5.

Nature 448, 539-540 (2 August 2007) | doi:10.1038/448539a; Published online 1 August 2007

Neurology: An Awakening

Michael N. Shadlen & Roozbeh Kiani

Neuroscientists and engineers are developing ways to help patients overcome paralysis and stroke. But what about mental function itself? Can medical intervention restore consciousness?

Jean-Paul Sartre wrote1: "In one sense choice is possible, but what is not possible is not to choose." To the neurologist, however, gaining consciousness is a decision of the unconscious brain to make choices. Philosophers and scientists may argue about the definition of consciousness2, 3, but neurologists have little trouble identifying its absence. Now, physicians are beginning to understand how it can be restored in some patients with severe brain damage. A case report by Schiff et al. (page 600 of this issue4) raises hope in this area, and sheds light on the neurobiological underpinnings of consciousness. Schiff and his colleagues treated a patient who had been in a 'minimally conscious state' (Box 1) for several years after a serious brain injury.

Sadly, the vast majority of coma patients do not recover consciousness. The prognosis is determined by the type of injury to the brain, its extent, and the findings from serial neurological examinations5. For example, a trained neurologist can predict with near certainty that meaningful recovery will not occur for many patients who remain in a coma for days after a cardiac arrest, in which the brain is deprived of blood flow and oxygen. For other patients, however, the outcome is less certain.

Even after severe brain injury, some patients retain enough of the cerebral cortex to raise hopes that some degree of organized mental function might one day recover. Indeed, some show intermittent signs that are clearly distinguishable from coma, despite an overall level of function that is effectively unresponsive. For these patients, we do not have reliable indicators of prognosis, and we lack treatments that might help the brain restore consciousness.

But advances in basic neuroscience are beginning to reveal the brain systems that are responsible for monitoring and sustaining engagement with the world around us. A key component is the thalamus, which lies between the brainstem and the cerebral hemispheres, and forms the gateway to the brain's cortex. NeurologyAn awakening

The thalamus is organized as a set of nuclei. The best understood of these nuclei are those containing the neurons that relay information from the eyes, ears and skin to the appropriate sensory cortex. But much of the thalamus is poorly understood. Anatomical studies in non-human primates have identified a class of thalamic neuron that might operate more generally in activating cortical networks6. These neurons, which stain positively for the calcium-binding protein calbindin, are found in all thalamic nuclei. Although we know little about the physiological properties of these calbindin-positive cells, they tend to exhibit a different pattern of connections with the cortex compared with the relay cells. Their axons terminate more broadly both across cortical areas and in layers that the relay cells miss. These calbindin-positive cells comprise a large percentage of the intralaminar nuclei of the thalamus — nuclei that have long been thought to have a role in arousal.

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6.

Nature 448, 542-544 (2 August 2007) | doi:10.1038/448542a; Published online 1 August 2007

Microbiology: The Inside Story

Laurie E. Comstock

The human intestine is home to trillions of bacteria. Investigation of the colonization of the infant gut by these microorganisms is a prelude to understanding how they may act in both health and disease.

At birth, babies emerge from a sterile environment into one that is laden with microbes. The infant's intestine then rapidly becomes home to one of the densest populations of bacteria on Earth. Writing in PLoS Biology, Palmer et al.1 report the most comprehensive analysis to date of the bacteria that first take up residence in the human intestine.

Interest in this ecosystem stems in part from the discovery of numerous benefits that arise from our intestinal microbiota: these bacteria help in extracting nutrients from food, and are instrumental in the development of the gut2, 3 and the immune system4 after birth. However, gut microbes have also been linked to several disease states, including inflammatory bowel diseases and colon cancer, and less directly to maladies such as asthma, rheumatoid arthritis, atopic dermatitis and even autism5, 6. An accurate and comprehensive analysis of the microbes present in the developing microbiota of the infant is an essential first step towards understanding which of them may affect the health of the host.

Palmer et al.1 analysed the microbial composition of the intestinal ecosystem of 14 infants by sampling their faeces. Sampling began with the first stool after birth, and was followed by 25 further samples from each infant over their first year of life. The authors' method of quantifying the bacterial composition avoided the need to culture the bacteria. It involved use of a comprehensive DNA microarray that differentiated and quantified the distinct taxonomic groups present in the samples.

There are 22 broad taxonomic groupings, or phyla, of bacteria, but the bacteria abundant in the infant intestine fell into only three of them: the Gram-positive bacteria (Firmicutes and Actinobacteria), the Bacteroidetes and the Proteobacteria. Given the broad nature of these taxonomic groupings, the results are not entirely surprising — most of the bacteria known to associate with humans fall into these three major groupings. A previous analysis of the intestinal microbiota of healthy adults demonstrated the abundance of only two of these three phyla7, with members of the Proteobacteria being only minor components. Proteobacteria are facultative anaerobes — that is, they can grow in the presence or absence of oxygen. They may be early settlers that are necessary to create the reduced environment required for the ensuing colonization by obligate anaerobes, which require oxygen-free conditions.

Contrasting with the similarity in the infants' microbiota at the phylum level, Palmer et al. found a remarkable degree of species-level variation, especially during the first few months. Some species appeared only transiently; others persisted for weeks to months. In general, there was no discernible pattern of abundant species or temporal mode of acquisition of particular organisms in different individuals. The two infants whose microbiotas were the most similar to each other were fraternal twins. These babies share both similar genetics and a similar environment. But their microbial profiles were no more like those of their own parents than they were to those of the parents of the other infants, implying that environment may play a greater role than genetics.

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7.

Nature 448, 548-549 (2 August 2007) | doi:10.1038/448548a; Published online 1 August 2007

Genomic Biology: The Epigenomic Era Opens

Stephen B. Baylin & Kornel E. Schuebel

Readout of information from the genome depends on intricate regulation of how DNA is packaged by proteins. The great endeavour to reveal how this packaging operates pan-genomically is now under way.

A new era is opening for biologists involved in understanding cellular systems. It is exemplified by papers by Mikkelsen et al. (page 553 of this issue)1 and Barski et al. (published in Cell)2 — they describe the kind of unprecedented insights that are emerging from investigations of how a single mammalian genome can be regulated to produce different cell types.

The technical and biological advances described in these studies extend the remarkable accomplishments of elucidating the structure3, then the sequence4, 5, of the human genome; and they reflect a growing, 'post-genomic', appreciation of the complexities of genome structure and function (Fig. 1). The intriguing — and daunting — challenge now is to understand the process of how and when specific DNA regions are controlled to produce the cellular diversity that underpins the development and maintenance of a single organism.

Central to this challenge is the task of enumerating the dizzying number of proteins interacting with the genome, and the functions they subserve. These proteins, called histones, form a combination with DNA that is termed chromatin. It is chromatin that provides the software packaging for the readout of the DNA hard drive. If alterations in genome heritable states occur through a change in the hard drive (that is, through a change in the primary sequence of DNA), a genetic alteration or mutation has occurred. This contrasts with an epigenetic change, which is an alteration in the heritable states of DNA function produced by altering the chromatin software. Epigenetic changes lie at the heart of how organisms generate different types of tissue under different circumstances — in embryonic development, in regulating cell renewal in adults, and in the cellular responses of the organism to environmental factors and stress. Moreover, disease states such as cancer are associated with a combination of both genetic and epigenetic abnormalities.

The central unit of chromatin is the nucleosome, which is constructed from short regions of DNA wound around an octet of histone proteins. This unit can modulate the readout from DNA in at least three ways.

First, nucleosomes can be physically re-arranged on DNA by complexes known as chromatin-remodelling proteins6 — generally, the greater the distance between nucleosomes, and so the 'openness' of chromatin, the higher the likelihood that such regions of DNA will be transcribed into RNA. Second, many nucleosomes can be compacted into higher-order aggregates to form 'closed' chromatin, or heterochromatin6, thereby preventing transcription. The balance between the open and closed parts of the genome facilitates proper gene-expression patterns in given cell types, and also prevents unwanted gene transcription.

Third, there is a complex interplay between enzymes that can modify particular amino acids in the histone component of the nucleosomes, and those that reverse the modifications. The modifications, or histone 'marks', interact with proteins that bind to and interpret them. The marks were initially seen as a 'histone code', the idea being that a restricted number of them would specify the 'on' or 'off' state of RNA production from DNA7. This concept was a most useful starting point. But it is increasingly recognized that the constituents of chromatin, and nucleosome structure, position and modification, are highly complex. It is a balance between these factors that marks an individual gene, or groups of genes, for various levels and states of expression8. That is, there is no simple on–off code.

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8.

Nature 448, 550-552 (2 August 2007) | doi:10.1038/448550a; Published online 1 August 2007

Biodiversity: Climate Change and the Ecologist

Wilfried Thuiller

The evidence for rapid climate change now seems overwhelming. Global temperatures are predicted to rise by up to 4 °C by 2100, with associated alterations in precipitation patterns. Assessing the consequences for biodiversity, and how they might be mitigated, is a Grand Challenge in ecology. BiodiversityClimate change and the ecologist

How serious is climate change compared with other factors affecting biodiversity?

Very — but it tends to act over a longer timescale. The ecological disruption wrought by climate change is generally slower than that caused by other factors. Such factors include habitat destruction through changes in land use; pollution, for example by nitrogen deposition; the invasion of ecosystems by non-native plant and animal species (biotic exchange); and the biological consequences of increased levels of carbon dioxide in the atmosphere (Fig. 1, overleaf). In the short-to-medium term, human-induced fragmentation of natural habitat and invasive species are particular threats to biodiversity. But looking 50 years into the future and beyond, the effects of climate are likely to become increasingly prominent relative to the other factors.

What are the effects of climate change?

Most immediately, the effects are shifts in species' geographical range, prompted by shifts in the normal patterns of temperatures and humidity that generally delimit species boundaries. Each 1 °C of temperature change moves ecological zones on Earth by about 160 km — so, for example, if the climate warms by 4 °C over the next century, species in the Northern Hemisphere may have to move northward by some 500 km (or 500 m higher in altitude) to find a suitable climatic regime. Higher temperatures are likely to be accompanied by more humid, wetter conditions, but the geographical and seasonal distribution of precipitation will change. Summer soil moisture will be reduced in many regions such as the Mediterranean basin, thus increasing drought stress. Overall, the ability of species to respond to climate change will largely depend on their ability to 'track' shifting climate through colonizing new territory, or to modify their physiology and seasonal behaviour (such as period of flowering or mating) to adapt to the changed conditions where they are.

What about the effect of atmospheric gases?

Carbon dioxide is, of course, known as one of the main drivers of the greenhouse effect, and so of increasing temperatures. But it is also essential for green-plant photosynthesis. Increased atmospheric CO2 results in an increase in photosynthesis rates (through CO2 fertilization), which could potentially balance the effect of temperature increase. This has the largest effect in regions where plant growth is limited by the availability of water, and will probably alter the competitive balance between species that differ in rooting depth, photosynthetic pathway or 'woodiness', as well as the subterranean organisms associated with them. Likewise, an increase of anthropogenic atmospheric nitrogen deposition affects nitrogen-limited regions (temperate and boreal forests, and alpine and Arctic regions) by conferring a competitive edge on plants with high maximum growth rates.

Which ecosystems are we talking about?

All of them, but climate change will affect them in different ways. For example, in marine ecosystems the possible consequences include increased thermal stratification (in which temperature differences separate water layers), reduced upwelling of nutrients, decreased pH and loss of sea ice. These changes will influence the timing and extent of the spring bloom of phytoplankton, and so the associated food chain (krill to fish to marine mammals and birds). On the terrestrial side, deserts, grasslands and savannahs in temperate regions are likely to respond to changes in precipitation and warming in various ways. Mediterranean-type ecosystems, which occur worldwide and are characterized by shrublands, are especially sensitive, as increased temperature and drought favour development of desert and grassland. In tropical regions, CO2 fertilization — in which plants absorb carbon from the atmosphere — and altered patterns of naturally occurring fires will have a strong influence. On tundra, low-growing plants are especially important as habitats for other organisms: their poleward movement will have an ecosystem-wide impact. Finally, species living on mountains are particularly sensitive to changed conditions, in that migration upwards can occur to only a limited extent.

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