ScienceWeek July 21, 2007
Dan Agin
July 21, 2007
Vol. 11 - Number 28
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In physics, instead of saying, I have explained
such and such a phenomenon, one might say, I have
determined causes for it the absurdity of which
cannot be conclusively proved.
-- Georg Christoph Lichtenberg (1742-1799)
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Contents (full text below):
1. Neuroscience: Brainwashing, Honeybee Style
2. Microbiology: Life on the Thermodynamic Edge
3. Stem Cells: The Magic Brew
4. Quantum Mechanics: Interference in the Matter
5. Neurobiology: New Order for Thought Disorders
6. Theoretical Physics: Walk the Planck
7. Cosmology: Unseen Universe: Welcome to the Dark Side
8. Cosmology: Unseen Universe: A Constant Problem
9. Book Review: The Social Life of Opium in China
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1.
Science 20 July 2007: Vol. 317. no. 5836, pp. 326 - 327 DOI:
10.1126/science.1144895
Neuroscience: Brainwashing, Honeybee Style
C. Giovanni Galizia
In the 1932 novel Brave New World, Aldous Huxley created a
society where fetuses develop in bottles and are treated with
chemicals to modify their bodies and mentalities (1). Later,
children are sleep-conditioned to their future task in society.
This procedure creates people who have clear roles, putting them
in castes, ranging from alphas (the leaders) to epsilons (the
drones). Among other things, lower castes are programmed not to
be aggressive against higher caste members. A treatment with
neurotoxic chemicals (including alcohol) during development leads
to the appropriate brain changes. On page 384 of this issue,
Vergoz et al. (2) elucidate some of the chemical cues that
influence learning and development in an actual animal caste
system--the honeybees.
Within the animal kingdom, social insects have evolved the most
stable caste societies. Many ant species have a wide range of
castes, from workers to foragers, from groomers to soldiers (3).
Individuals all develop from eggs laid by the same mother--the
colony's queen. Generally, the food supplied to each egg is the
biological signal that leads the embryo to develop into one caste
or another, a situation reminiscent of Huxley's fictional world.
Thus, if we take as an example the leaf-cutter ant Atta texana,
small individuals tend to the fungus garden within the nest,
intermediate-sized individuals search and collect leaves from the
forest to feed the fungus, and large individuals with strong
mandibles defend the colony.
Honeybees have evolved a different caste system: The individual
worker bees (always females, because male drones do not
contribute to social life apart from mating with queens during
nuptial flights) perform different tasks in the course of their
lives. The workers start off as nurses tending to the hive right
after emergence, continue with tasks such as nest-building and
hive defense, and then end their lives as foragers by collecting
nectar and pollen to make honey and feed their sisters.
How is this developmental polyethism organized? Age is the main
factor that determines the task that an individual will perform,
mediated by regulation with juvenile hormone (4), but feedback
from the hive is also important. Much information is delivered by
pheromones. For example, when a hive loses the queen, her queen
mandibular pheromone (QMP) will also disappear, leading to rapid
changes in behavior among the worker bees, who start raising new
queens to replace her.
However, the life of a honeybee is not hard-wired. Bees are
amazingly intelligent animals and learn a lot about their
environment. In particular, forager bees learn color, odor, and
position of nectar-rich flowers and use this information to
optimize their harvest. This capacity has been used for many
years to learn more about the basic mechanisms underlying
appetitive (i.e., food-related) learning and memory, and the
honeybee has become an important model animal to this end (5).
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2.
Science 20 July 2007: Vol. 317. no. 5836, pp. 327 - 328 DOI:
10.1126/science.1145970
Microbiology: Life on the Thermodynamic Edge
Edward F. DeLong
Microbial life can persist under physicochemical conditions that
challenge the very fabric of biological structure and function.
In habitats of extreme temperatures, pH's, and salinities,
microbes are often the sole inhabitants. But microbial life also
exists at another type of extreme: under conditions that yield
barely enough free energy for cell maintenance, much less growth.
In a recent study of the full genome sequence of the anaerobic
bacterium Syntrophus aciditrophicus, McInerney et al. (1)
reported new insights into some of the fundamental machinery
required for living at life's thermodynamic edge.
S. aciditrophicus grows mainly by a symbiotic process known as
syntrophy--a metabolic cooperation usually involving two
anaerobic microbes, in which each partner depends on the other
for growth on a specific substrate (2). For example, S.
aciditrophicus can efficiently degrade fatty acids or benzoate in
the absence of oxygen, but only when a syntrophic partner
(typically a hydrogen-consuming methanogen or sulfate-reducing
bacterium) is around to consume its metabolic waste products (3).
Symbiotic hydrogen removal shifts the chemical equilibria,
thereby yielding sufficient metabolic free energy for S.
aciditrophicus to grow while simultaneously feeding its
syntrophic partner with energy-rich growth substrates like
hydrogen or formate (see the figure). Alone, neither partner can
grow well on benzoate anaerobically; the thermodynamics for
growth are favorable only when the partners engage in metabolic
cooperation (4, 5).
The genome sequence of S. aciditrophicus (1) provides new insight
into the details of this unusual anaerobic life-style. As
expected, the genome encodes little potential for a respiratory
metabolism using external terminal electron acceptors like
oxygen, nitrate, fumarate, sulfate, or iron. It also lacks many
of the genes required for fermentation, the other main pathway
for balancing oxidizing and reducing potential in the absence of
oxygen. Instead, S. aciditrophicus is dependent on the electron-
consuming activities of its partners as its primary terminal
electron sink.
Although S. aciditrophicus cannot grow on compounds like starch
or sugars, it contains four different alpha-amylase genes
encoding proteins that hydrolyze starch. Perhaps it not only
feeds hydrogen to other downstream syntrophic partners, but also
assists its fermentative neighbors further up the anaerobic food
chain in the initial steps of polysaccharide hydrolysis. This
could help to ensure that fatty acids--the preferred growth
substrate of S. aciditrophicus--are supplied as the waste
products of its sugar-fermenting cohorts. Such potential for
metabolic cooperation both upstream and downstream in the
anaerobic food chain emphasizes the fact that many (and perhaps
most) microbial metabolic and biogeochemical transformations in
nature require coordinated, synergistic interactions within
microbial communities.
Adenosine triphosphate (ATP) is the common energy currency of all
cellular life. One of the functions of energy metabolism is to
ensure an adequate supply of this biochemical fuel. Surprisingly,
S. aciditrophicus lacks the genes for acetate kinase, one of the
central enzymes anaerobes typically use to produce ATP via a
substrate-level phosphorylation. However, the presence of nine
genes that code for the enzyme acetyl-coenzyme A synthetase
suggests that S. aciditrophicus employs an alternative reaction
also used by acetate-forming Archaea and by anaerobic Eukarya to
produce ATP.
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3.
Nature 448, 260-262 (19 July 2007) | doi:10.1038/448260a;
Published online 18 July 2007
Stem Cells: The Magic Brew
Janet Rossant
Researchers have engineered embryonic stem-like cells from normal
mouse skin cells. If this method can be translated to humans,
patient-specific stem cells could be made without the use of
donated eggs or embryos.
Two reports in this issue1, 2 and one elsewhere3 describe a
seemingly simple method for changing differentiated adult cells
into pluripotent stem cells. The 'gold-standard' test for
pluripotency is the ability of a cell to contribute extensively
to all adult cell types, including the germ line. The cells
generated by these authors pass this test. The researchers
introduced four gene-transcription factors into fibroblast cells
originating from mouse skin, and specifically selected those
cells that, in response to these factors, expressed genes
indicative of a pluripotent state. Not only did all three teams
manage to isolate cell lines that resembled mouse embryonic stem
(ES) cells, but when they injected these cells into early
embryos, the cells differentiated into all normal adult cell
types.
A previous study4 had shown that differentiated adult cells could
be transformed into pluripotent cells when fused with ES cells.
This hinted that factors found in ES cells might be essential to
conferring pluripotency on other cells. However, the
transcriptional profiles, modifications to chromatin (complexes
of DNA and histone proteins) and DNA methylation status of ES
cells are very different from those of adult cells, indicating
that pluripotency is probably under complex layers of control. It
was, therefore, a surprise when Takahashi and Yamanaka5 reported
last year that they could produce cell lines with some of the
properties of ES cells by introducing just four transcription
factors associated with pluripotency - Oct3/4, Sox2, c-Myc and
Klf4 - into mouse skin fibroblasts, and then selecting cells that
expressed a marker of pluripotency, Fbx15, in response to these
factors. These cells were called induced pluripotent stem (iPS)
cells.
However, the generated iPS cells differed from ES cells in their
gene-expression and DNA-methylation patterns. And when these
cells were injected into normal mouse blastocysts (70-100-cell
embryos), no live chimaeras - animals carrying cells throughout
their bodies from both the original blastocyst and from iPS cells
- were born.
Yamanaka and colleagues1, as well as Wernig et al.2 and Maherali
et al.3, surmised that if selection of iPS cells were based on
the expression of genes that are more essential for pluripotency
than Fbx15, this might improve the generation of truly
pluripotent reprogrammed cells. They derived embryonic or adult
fibroblasts that were engineered to express drug-selectable
markers under the control of one or other of the two best-studied
genes crucial for pluripotency - Nanog and Pou5f1 (Fig. 1). After
introducing the four factors (Oct3/4, Sox2, c-Myc and Klf4) by
the technique of retroviral transfection, cells were subjected to
drug selection. All three groups could derive stable cell lines.
In terms of transcriptional, imprinting (expression of alleles
predetermined by the parent from which they originated) and
chromatin-modification profiles, these were essentially identical
to ES cells. Maherali et al.3 also report appropriate
reactivation of the inactivated X chromosome in a female iPS cell
line, and all authors present images of chimaeric mice, as well
as evidence of germline transmission of the genetic content of
iPS cells.
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4.
Nature 448, 262-263 (19 July 2007) | doi:10.1038/448262a;
Published online 18 July 2007
Quantum Mechanics: Interference in the Matter
Markus Kindermann
Like any particle, electrons are also waves that can interfere
with each other. Remarkably, this interference can even happen
between electrons from different sources that have never
physically interacted.
That electrons are waves can be conclusively demonstrated by
sending them through two parallel slits, and observing the
interference patterns between them that result as they diffract.
Such double-slit experiments led a recent ranking of the most
beautiful experiments in the history of physics1. They were first
performed with electrons in free space2, but similar experiments
performed later showed that the wave character also extends to
electrons in small metallic conductors at very low temperatures3.
Neder et al.4, whose results appear on page 333 of this issue,
have moved on to a next level: they have demonstrated
compellingly that electron waves can interfere even if they
originate from independent sources.
The statement that classical electromagnetic waves always add up
('superpose') no matter where they come from is quite intuitive,
and typically taken for granted. The waves emitted by different
light sources are thus able to interfere. This interference can
even be observed for sources that are incoherent, or out of
phase, through a phenomenon known as the Hanbury Brown-Twiss
effect5.
The same assertion made of electron waves is less obvious. The
natural inclination is to describe each electron by its own
matter wave that is independent of the waves associated with
other electrons. And electrons with different origins are, one
might think, evidently different.
This last assumption in fact turns out to be flawed. All
electrons are intrinsically identical, and there is nothing
besides their state at any particular moment that distinguishes
two electrons (or any two elementary particles of the same kind)
from each other. This is one of the fundamental postulates of
quantum mechanics, and it follows that all electrons in the
Universe are described by the same matter wave that invisibly
connects them.
This strange fact has profound consequences. One of these is the
phenomenon of 'anti-bunching': electrons tend to avoid getting
too close to each other in space. Anti-bunching has been
demonstrated with electrons in free space6 and in electrical
conductors7, 8. But Neder and colleagues' painstaking
demonstration of the interference of electron waves from
independent sources4 beautifully shows the fundamental mechanism
underlying the anti-bunching phenomenon.
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5.
Nature 448, 263-265 (19 July 2007) | doi:10.1038/448263a;
Published online 18 July 2007
Neurobiology: New Order for Thought Disorders
Lorna W. Role & David A. Talmage
Can we really learn about complex human psychiatric disorders
through genetic manipulations in mice? Yes, according to studies
of how altering the gene encoding neuregulin 1 affects signalling
in the mouse brain.
Schizophrenia is a spectrum of disorders. Its causes lie in a
complex interplay of genetic, prenatal and developmental factors,
as well as precipitating events in later life. Given the
complexity of this uniquely human disorder, surely it is hubris
to think that poking around at a rodent gene or two could shed
light on the processes underlying it? Results from Li et al.1 and
Woo et al.2, published in Neuron, suggest not. Building on a link
first made in 2002 between schizophrenia and a protein called
neuregulin 1 (Nrg1) and its signalling partners, the ErbB
receptors3, 4, these authors highlight how targeted manipulation
of Nrg1 in mice can help to illuminate the workings of neural
circuits gone awry.
The devastating array of psychotic, emotional and cognitive
symptoms that comprise schizophrenia is thought to be caused by
an imbalance in the fine tuning, or 'synaptic plasticity', of
connections between neurons in the brain. This plasticity
reflects the ability, in healthy individuals, to adjust, adapt
and alter the levels of excitability of the myriad synapses and
circuits that link different brain regions in a manner precisely
coupled to ever-changing demands.
Li et al.1 and Woo et al.2 use a range of techniques to
manipulate the levels of Nrg1-ErbB signalling with high precision
in space and time. They examine the effects of this regulation on
different electrical, neurochemical and morphological measures of
synaptic plasticity and reach two fundamental conclusions: first,
that synaptic plasticity requires precisely the correct level of
Nrg1-ErbB signalling; and second, that the absolute levels of
Nrg1-ErbB signalling are regulated by different patterns and
intensities of neural activity. Thus synaptic plasticity is held
in critical balance by bidirectional Nrg1-ErbB signalling between
neurons on either side of the synapse, and between these neurons
and their supporting cells, called glia.
Li et al.1 examine the role of Nrg1-ErbB signalling in the
hippocampus, the brain region in which learning and memory is
best established. The long-term activation ('potentiation') and
depression of synaptic connections within the hippocampus - in
particular between the CA1 and CA3 subregions studied by Li and
colleagues - manifest themselves in changes in the number and
strength of the synapses, and depend crucially on the activation
of various types of receptor for their neurotransmitter,
glutamate. The authors' selective manipulation of levels of Nrg1
expression in CA3 and ErbB in CA1 demonstrates that the long-term
potentiation of connections between CA3 and CA1 requires both
presynaptic Nrg1 and postsynaptic ErbB (Fig. 1). If either of
these components is missing, glutamate-mediated transmission is
impaired, and classic methods for inducing long-term potentiation
elicit only transient activation.
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6.
Nature 448, 257 (19 July 2007) | doi:10.1038/448257a; Published
online 18 July 2007
Theoretical Physics: Walk the Planck
Giovanni Amelino-Camelia
Where relativity and quantum mechanics clash, new laws of physics
should emerge.
The Planck scale is where general relativity and quantum
mechanics should clash. It is the realm of the unfeasibly
energetic and the unimaginably tiny. It is where the laws of
nature are expected to achieve their highest level of elegance
and simplicity - and where speculation abounds.
Albert Einstein's general theory of relativity follows a
completely different logic from quantum mechanics. In relativity,
observables evolve smoothly and deterministically. Quantum
mechanics, in contrast, relies on quanta and probabilistic
predictions.
Mostly, these differences are moot. Quantum mechanics describes
the interactions of microscopic entities, such as the low-energy
particles typically studied in laboratories. Here, general
relativity can be ignored because the electroweak and
electrostrong forces far outweigh gravitational forces. General
relativity takes centre stage for the motions of macroscopic
bodies such as planets. Here gravitational interactions dominate,
because the bodies are composed of a large number of particles;
the electroweak and electrostrong forces can be disregarded
because they tend to average out.
Around the Planck scale - equivalent to 1019 gigaelectronvolts -
things get tricky. For microscopic particles with energy this
high or higher, both quantum-mechanical and general-relativistic
effects come into play. Gravity enters the picture, in other
words.
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7.
Nature 448, 240-245 (19 July 2007) | doi:10.1038/448240a;
Published online 18 July 2007
Unseen Universe: Welcome to the Dark Side
Jenny Hogan
Physicists say that 96% of the Universe is unseen, and appeal to
the ideas of 'dark matter' and 'dark energy' to make up the
difference. In the first of two articles, Jenny Hogan reports
that attempts to identify the mysterious dark matter are on the
verge of success. In the second, Geoff Brumfiel asks why dark
energy, hailed as a breakthrough when discovered a decade ago, is
proving more frustrating than ever to the scientists who study
it.
We're underneath 1,400 metres of Italian mountain, walking
through cavernous halls that lead from a 10-kilometre-long road
tunnel. The scientists working within the Gran Sasso National
Laboratory near L'Aquila seem ant-like in scale against the
backdrop of vast metal spheres, towers and scaffolding that house
their underground experiments. Physicist Elena Aprile is hurrying
the group along, pointing out one project after another. She
stops to take a photo of one, exclaiming at its size. We finally
reach Aprile's XENON10 experiment, which is tucked away at the
end of a small side tunnel. This is the project into which Aprile
has poured her energy over the past few years, one of several
experiments at Gran Sasso and around the world that are waiting
for a passing piece of 'dark matter' to show itself.
Once upon a time, waiting for new particles to reveal themselves
was a major endeavour. Scientists in the 1940s would also head to
the mountains - to their tops, not to underground caverns -
carrying emulsion-covered plates to capture strange new cosmic
rays. But as particle accelerators became more powerful,
physicists became adept at making their own novelties, and lying
in wait for chance discoveries fell out of fashion. In this,
dark-matter searches are something of a throwback.
They are a reminder of the past in another way, too. Ever more
powerful accelerators require ever vaster detectors and ever
larger teams of people to make sense of their output. The Large
Hadron Collider (LHC) under construction at CERN, the European
particle-physics laboratory just outside Geneva, will cost euro
dollar3 billion (US$4.1 billion) and is the work of thousands of
scientists and engineers. The XENON10 detector is run by just 30
scientists, and that's part of its attraction. "It's a last
chance to do physics like it used to be done," says Aprile.
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8.
Nature 448, 245-248 (19 July 2007) | doi:10.1038/448245a;
Published online 18 July 2007
Unseen Universe: A Constant Problem
Geoff Brumfiel
Why is dark energy, hailed as a breakthrough when discovered a
decade ago, proving so frustrating to the scientists who study
it?
In 1998, two teams of astronomers reported that the Universe was
pulling itself apart. This came as something of a shock. That the
Universe was expanding had been known since the 1920s, but
conventional wisdom held that this expansion was slowing and was
likely, in the distant future, to come to an all but complete
halt. Then, in the late 1990s, observations of distant supernovae
showed that the expansion was not slowing down at all. It was
speeding up. This discovery was incredibly counterintuitive,
recalls Charles Bennett, an astronomer at Johns Hopkins
University in Baltimore, Maryland. "I just didn't believe it."
Within a few years, however, he and almost all his peers could
withhold their belief no longer. The observations became
stronger. And the expansion provided a way out of a theoretical
impasse. Observations of the Big Bang's afterglow made by various
groups, including Bennett's, indicated that the Universe's
gravity had flattened it out. But other observations suggested
that it simply didn't contain enough matter to have that much of
a gravitational effect - even when as-yet-undiscovered forms of
dark matter were included in the sums (see page 240).
Happily, the theory of relativity requires energy, as well as
matter, to have a gravitational effect. And it turned out that
the amount of energy needed to drive the acceleration was pretty
close to that needed to solve the flatness problem by means of
its gravity. 'Dark energy', as it quickly became known, seemed
poised to provide great insight into the origin and future of the
cosmos, says Michael Turner, a cosmologist at the University of
Chicago in Illinois. "This seemed to be the piece that made
everything else work."
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9.
Social History of Medicine 2007 20(1):182-183;
doi:10.1093/shm/hkm020
Book Review: The Social Life of Opium in China. Zheng Yangwen.
Cambridge University Press, 2005. Pp. 256 ISBN 0521846080.
This book is a fascinating study of the social and cultural
dimensions of opium use in China. Zheng Yangwen draws on a wide
range of Chinese and English language sources to reconstruct the
history of the spread of opium consumption, the dissemination of
knowledge about the drug and its incorporation into the everyday
lives of almost all sections of society by the nineteenth
century. Whereas there is a vast literature on the opium trade,
especially for the colonial period, attention has been recently
refocused on the ways in which opium penetrated and impacted upon
societies and cultures in Asia. The early south-east Asian
history of the substance is particularly obscure. In
reconstructing the social life of opium, Zheng also provides us
with a valuable account of its pre-colonial past in China.
Citing sources from the late Ming period, Zheng dates the
introduction of opium into China to the latter half of the
fifteenth century. It is generally recognised that opium as a
narcotic has an eastern Mediterranean origin. Long-distance Asian
trading networks in the pre-modern period would have enabled
transmission of knowledge about the properties of the drug across
the Indian Ocean and overland along the Silk Road. During the
late pre-colonial period, the opium poppy was being cultivated in
several parts of Iran, Afghanistan and India. It is therefore
unlikely that opium, at least as a medicine, was entirely unknown
to the Chinese, the more so because of its reputation as a potent
pain-killer. The substance appeared among the various exotic
items offered as tribute to the emperor in the Ming period. It
would appear that by the end of that dynasty, and at the
commencement of Qing rule (c. mid-seventeenth century), the
uppermost sections of the ruling elite were quite familiar with
opium.
The combination of the cultures of tobacco, another novel
substance, and opium gave rise to opium-smoking, the form in
which the drug was usually consumed in China. During the course
of the eighteenth century, opium consumption became widespread in
China as a result of aggressive marketing of the drug in south-
east Asia by the Dutch and subsequently by the English. It is
significant that unlike, for instance, India, where poppy
cultivation was also introduced relatively late (sometime during
the medieval period), there is little evidence of local
production in the early Qing period. This would confirm the view
that opium was not a traditional mood-altering substance in
China, and that the real jump in consumption came during the
latter half of the eighteenth century as a result of the
commercial policies of the English East India Company. They were
successful because the substance was novel, and as such Chinese
society lacked adequate cultural devices for restricting its
recreational use.
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