ScienceWeek August 4, 2007

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SCIENCEWEEK

August 4, 2007

Vol. 11 - Number 30

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

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)

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

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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