ScienceWeek June 22, 2007
Dan Agin
June 22, 2007
Vol. 11 - Number 24
--------------------------------
I would live to study, and not study to live.
-- Francis Bacon (1561-1626)
--------------------------------
Contents (full text below):
1. Genetics: A Breakthrough for Global Public Health
2. Psychology: Birth Order and Intelligence
3. Immunology: Short-Term Memory
4. Materials Science: Reflections on Ionic Liquids
5. Evolutionary Biology: Re-Crowning Mammals
6. Eukaryote Evolution: Engulfed by Speculation
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
1.
Science 22 June 2007: Vol. 316. no. 5832, pp. 1703 - 1704 DOI:
10.1126/science.1138904
Genetics: A Breakthrough for Global Public Health
D.D. Chadee et al
The reemergence of dengue fever and urban yellow fever in the
Americas during the past 20 years demonstrates that mosquito-
borne diseases are threats even in the 21st century. Globally,
about 50 million to 100 million cases of dengue and about 500,000
cases of dengue hemorrhagic fever occur annually (1). Recently,
an unprecedented chikungunya virus outbreak occurred in countries
bordering the Indian Ocean, with ~250,000 cases and 205 deaths.
The threat of mosquito-borne pathogens is very real, with dengue,
yellow fever, and chikungunya viruses all being transmitted by
the mosquito Aedes aegypti.
Nene et al. report the complete genome sequence of Ae. aegypti
(2). This comes about 4 years after the complete genome sequence
of Anopheles gambiae, the primary mosquito vector of malaria in
Africa (3). It is also a little over 100 years since Ae. aegypti
was shown to transmit yellow fever. As the blueprint for the
vector's biology, the Ae. aegypti genome sequence is another
major advance in the history of combating mosquito-borne disease.
Mosquito-borne disease control is currently based on clinical
management of patients and mosquito control because efficient
vaccines are unavailable. The challenge ahead is to use genome
sequence information to understand gene and protein functions and
the causes of mosquito diversity that determine the role of Ae.
aegypti in pathogen transmission (4).
The completed sequence should greatly facilitate the
identification of Ae. aegypti genes and proteins that control a
wide range of traits such as vector competence and capacity for
pathogen transmission, life history, olfactory cues that affect
behavior, host seeking, mating behavior, and insecticide
resistance. The genome sequence should also help identify new DNA
markers and allow DNA fingerprinting for ecological studies. Such
tools are essential to characterize both individual mosquitoes
and natural populations of Ae. aegypti. Genetic characterization
of mosquito populations should reveal how pathogen transmission
is influenced by gene flow, geographic isolation, and population
dynamics and dispersal. Moreover, characterizing gene variation
in natural populations will provide a basis for understanding the
risk for Ae. aegypti-borne epidemics. For example, yellow fever
has never been reported in Asia, despite the presence of dengue
and Ae. aegypti. Such an epidemic would be a catastrophe.
Tools for genetically altering Ae. aegypti (or An. gambiae) can
now be more easily adapted for creating mosquitoes that are
pathogen-resistant (5). In combination with new information on
the effects of genes on the mosquito phenotype, deploying such
resistant mosquitoes should be possible. Endosymbiotic bacteria
could also be genetically modified to introduce desirable genes
into mosquito populations that reduce vector competence for a
pathogen or reduce their survival (6), a strategy guided by a
deeper understanding of Ae. aegypti biology through its genome
sequence.
The Ae. aegypti subspecies, Ae. aegypti aegypti and Ae. aegypti
formosus, differ in appearance, geographical distribution,
behavior, genetic diversity and relatedness, and vector
competence for yellow fever virus (7) and dengue virus (8). The
completed genome sequence is from Ae. aegypti aegypti because it
is widely distributed, is the primary vector, and likely evolved
from Ae. aegypti formosus (7). But the relationship between the
geographic distribution and genetic diversity of Ae. aegypti must
be clarified to ensure that control strategies are used that are
appropriate for the specific location. Genetic mapping studies
have implicated many genes in Ae. aegypti vector competence for
dengue virus (8). However, specific genes have not yet been
identified; the Ae. aegypti genome sequence should help in this
characterization. The An. gambiae genome sequence has been
essential to identifying candidate genes that control
susceptibility to malaria infection. This was accomplished
through the use of RNA interference, a technique that "knocks
down" the expression of specific gene targets in the organism
(9).
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
2.
Science 22 June 2007: Vol. 316. no. 5832, pp. 1711 - 1712 DOI:
10.1126/science.1144749
Psychology: Birth Order and Intelligence
Frank J. Sulloway
Research on birth order and intellectual performance is replete
with contradictory findings and long-standing conceptual
disagreements. In the wake of these ongoing controversies, a new
study that has profited from past debates is especially welcome.
In an elegantly designed analysis of 241,310 Norwegian 18- and
19-year-olds that appears on page 1717 of this issue, Kristensen
and Bjerkedal show that older siblings have higher intelligence
test scores than younger siblings (1). In addition, these two
researchers demonstrate that how study participants were raised,
not how they were born, is what actually influences their IQs.
In a companion study, Bjerkedal et al. (2) show that birth-order
differences in their Norwegian sample are nearly identical for a
subset of adjacent siblings who were raised together (127,902
individuals) and for a between-family sample (112,799
individuals). Critics have long argued that such birth-order
effects, which typically emerge in between-family studies, are
spurious--phantom artifacts of uncontrolled differences in family
size, socioeconomic status, parental IQ, and other background
factors (3-5). At least in the domain of intellectual ability,
the new Norwegian findings rule out this alternative explanation.
Critics might still argue that the mean IQ difference documented
between a Norwegian firstborn and a secondborn is only 2.3
points. Such a modest difference, however, can have far greater
consequences than most people realize. For example, if Norway's
educational system had only two colleges--a more prestigious
institution for students with IQs above the mean, and a less
desirable institution for all other students--an eldest child
would be about 13% more likely than a secondborn to be admitted
to the better institution (the relative risk ratio), and the odds
of a firstborn being admitted would be 1.3 times as great. In
medicine, new therapeutic benefits of this magnitude often make
front-page headlines. In addition, such differences in
opportunities gained or lost inevitably accumulate over one's
lifetime.
One puzzle highlighted by these latest findings is why certain
other within-family studies have failed to show equally
consistent results. Some of these previous null findings, which
have all been obtained in much smaller samples, may be explained
by inadequate statistical power, as Bjerkedal et al. themselves
suggest. But most previous researchers have overlooked another
intriguing reason for such inconsistent outcomes, which are
generally found in studies of children rather than adults. As has
been noted by Zajonc and colleagues, younger siblings tend to
score higher than older siblings when tests of intellectual
ability are conducted under the age of about 12 (6, 7). In more
than 50 previous samples, there is a significant tendency for IQ
disparities by birth order to reverse direction as children get
older.
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
3.
Nature 447, 916-917 (21 June 2007) | doi:10.1038/447916a;
Published online 20 June 2007
Immunology: Short-Term Memory
Benjamin N. Gantner & Harinder Singh
Chemical modification of histone proteins can affect the
expression of their associated genes. Some immune cells seem to
exploit this process to avoid excessive inflammation while
fighting invading pathogens.
The innate immune system has several essential roles: it must
detect infectious pathogens, initiate antimicrobial mechanisms to
remove them and trigger inflammation to activate additional
immune responses such as fever. This last function is tricky
because too little inflammation will lead to an ineffective
response and too much can lead to septic shock and death. So how
does the innate immune system prevent excessive responses while
repeatedly encountering the same pathogen during an infection?
It has been appreciated for some time that particular innate
immune cells - macrophages - can dampen their reactions; however,
on page 972 of this issue, Foster et al.1 suggest a more complex
change in the sensitivity of these cells to pathogens. They find
that macrophages selectively modify the histone proteins that
package the genes activated in response to pathogens, to adapt to
repeated exposure.
More than a century ago, Richard Pfeiffer discovered2 that
components of dead bacteria, which he called endotoxins, could
kill test animals; this is now known to be due to an excessive
inflammatory response. Endotoxins are highly conserved components
of pathogens that are recognized by the innate immune system.
Among the most potent endotoxins is lipopolysaccharide (LPS),
which is a component of the outer membrane of bacterial cells. It
is recognized by Toll-like receptor 4 (TLR4) on the surface of
macrophages, where it initiates the molecular signalling pathways
that lead to the activation of proinflammatory and antimicrobial
genes.
Paul Beeson's seminal work3 in the 1940s uncovered a fascinating
twist to the endotoxin response in humans. The typhoid vaccine
was used in patients with syphilitic infection of the nervous
system to slow disease progression. Although initial exposure to
this vaccine caused fever, repeated daily exposures suppressed
the induction of fever and led to a state of tolerance.
Similarly, macrophages, which underpin many of the physiological
responses to endotoxins, exhibit LPS tolerance on repeated
stimulation4. Consequently, through limiting the production of
proinflammatory molecules, tolerance is thought to provide a
mechanism for restraining systemic inflammation and avoiding
septic shock4.
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
4.
Nature 447, 917-918 (21 June 2007) | doi:10.1038/447917a;
Published online 20 June 2007
Materials Science: Reflections on Ionic Liquids
Robin D. Rogers
Ionic liquids are generally regarded as solvents, but these
modular, tunable compounds have far greater technological
potential. With a coat of silver, they become ideal materials for
the liquid mirror of a space telescope.
Ionic liquids seem to defy common sense. Most ionic compounds are
crystalline solids with high melting points, but these
fascinating salts melt at temperatures below 100 °C; indeed, many
are liquids at room temperature. Their melt forms are composed of
discrete cations and anions1 that can be individually customized,
allowing the synthesis of a wide range of liquid materials with
tunable physical, chemical and biological properties.
There are thought to be about a million possible pure ionic
liquids, and 1018 ternary liquid mixtures, so anyone designing
the perfect liquid material for a given application has a lot of
room for manoeuvre. A particularly striking example is described
by Borra et al.2 on page 979 of this issue. They have coated an
ionic liquid with colloidal silver particles, yielding a material
that could be used as a liquid mirror in a telescope.
Ionic liquids are not new3, but they have recently received
intense worldwide scrutiny as possible environmentally friendly
solvents4 because many are non-volatile. This has fuelled a
technological revolution, powered by the sheer number of
unstudied liquids that might be fine-tuned for specific purposes
(although the 'green' credentials of ionic liquids have been
questioned by reports that some of these compounds are toxic5).
It was, therefore, inevitable that new applications would emerge
from the growing number of scientific and technological
disciplines studying these liquids.
Ionic liquids are known for their distinct physical properties
(such as low or non-volatility, thermal stability and large
ranges of temperatures over which they are liquids6), chemical
properties (such as resistance to degradation, antistatic
behaviour, chirality and high energy density) and biological
activities (such as antimicrobial and analgesic properties7). But
what is less appreciated is that these properties in individual
ionic liquids can be combined in composite materials to afford
multifunctional designer liquids. It is therefore refreshing to
see a study2 that focuses on the unique attributes and uses of
ionic liquids, rather than on whether they are green or toxic.
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
5.
Nature 447, 918-920 (21 June 2007) | doi:10.1038/447918a;
Published online 20 June 2007
Evolutionary Biology: Re-Crowning Mammals
Richard L. Cifelli & Cynthia L. Gordon
The evolutionary history of mammals is being tackled both through
molecular analyses and through morphological studies of fossils.
The 'molecules versus morphology' debate remains both vexing and
vibrant.
On page 1003 of this issue, Wible and co-authors1 announce the
discovery of a well-preserved mammal from Mongolia dated at
between 71 million and 75 million years old. The fossil, dubbed
Maelestes gobiensis, is noteworthy in its own right: finds of
this sort are exceptional in view of the generally poor record of
early mammals.
More interesting, though, is what this fossil and others from the
latter part of the age of dinosaurs (the Cretaceous period, about
145 million to 65 million years ago) have to say about the rise
of mammalian varieties that populate Earth today. The authors
have gone much further than describing an ancient fossil
specimen, and present a genealogical tree depicting relationships
among the main groups of living and extinct mammals. Here, all
Cretaceous fossil mammals are placed near the base of the tree,
as dead 'side branches', well below the major tree 'limbs'
leading to living mammals. These results differ strikingly from
those of other recent palaeontological studies2, 3.
Chronologically speaking, this new analysis1 is eye-popping
because it places direct ancestry of today's mammals near the
Cretaceous-Tertiary (K/T) boundary about 65 million years ago.
This is much younger than dates based on molecular biology - for
example, a recent and comprehensive analysis by Bininda-Emonds et
al.4 pushed that ancestry back more than twice as far into the
geological past, to some 148 million years ago. The conflicting
results of these palaeontological1 and molecular4 studies have
profound implications for understanding the evolutionary history
of mammals, and for understanding the pace and nature of
evolution generally.
Three main groups of living mammal are recognized: the egg-laying
monotremes such as the platypus; marsupials (kangaroos, koalas,
opossums and so on); and placentals, which constitute the most
varied and diverse group, including everything from bats to
whales and accounting for more than 5,000 of the 5,400 or so
living mammals. Fossils can be placed within one of these three
'crown' groups only if anatomical features show them to be nested
among living species5.
The placental crown group, which is of primary interest here,
represents the living members of a more encompassing group,
Eutheria, which includes extinct allied species, the oldest of
which dates to about 125 million years ago6. Herein lies a
central problem: because of inadequate preservation and/or non-
comparability with living species, the affinities of many early
mammals have been contentious. Certain Cretaceous fossils have
been previously recognized as members of the placental crown
group; some analyses suggest the presence of placental
superorders in the Cretaceous2, 3, but referral of such ancient
fossils to living orders is dubious5. For context, placentals
encompass four major divisions, or superorders, each containing
one to six orders, such as Cetacea (whales), Primates and
Rodentia.
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
6.
Nature 447, 913 (21 June 2007) | doi:10.1038/447913a; Published
online 20 June 2007
Eukaryote Evolution: Engulfed by Speculation
Anthony Poole & David Penny
The notion that eukaryotes evolved via a merger of cells from the
other two domains - archaea and bacteria - overlooks known
processes.
In the absence of direct evidence, science should proceed
cautiously with conjecture. Geologist Charles Lyell (1797-1875)
warned us not to proceed like medieval scholars, who "often
preferred absurd and extravagant positions, because greater skill
was required to maintain them". Scientific speculation, Lyell
emphasized, must take known processes into account. This has not
happened with the debate on how eukaryotes (animals, plants,
fungi, protists) arose. The conflicting hypotheses currently on
offer show a curious disregard for mechanism.
One thing at least is agreed: the mitochondrion, powerhouse of
the eukaryote cell, evolved from an engulfed bacterium. The
question is 'who' did the engulfing. Did an archaeon engulf a
bacterium? Did a bacterium, bacterial consortium, or RNA cell
engulf first an archaeon (which became the nucleus) and then the
mitochondrial ancestor? Perhaps nuclei emerged in a virus-
infected archaeon, which then engulfed mitochondria. Which, if
any of these, is right?
In the mid-1990s, a somewhat pedestrian view of eukaryotic
origins, the 'archezoa hypothesis', held sway. This maintained
that a protoeukaryote (with nucleus) engulfed the mitochondrial
ancestor. Supporting the theory were 'archezoa', anaerobic
eukaryotes with no mitochondria. Archezoa apparently populated
the oldest branches of the eukaryote tree, suggesting that
eukaryotes began diversifying before mitochondria entered the
picture.
The archezoa hypothesis is thus composed of two independent
hypotheses: (a) that a protoeukaryote host (PEH) engulfed the
mitochondrial ancestor, and (b) that modern archezoa are 'missing
links' that never possessed mitochondria. Hypothesis (b) is now
unanimously rejected: every archezoan examined bears vestigial
mitochondria, or genes inherited from mitochondria. Thus, all
modern eukaryotes evolved from a mitochondrion-bearing ancestor.
But the baby was thrown out with the bath-water. Hypothesis (a)
was also rejected, and because eukaryotes and archaea share a
number of similar genes, the deposed PEH was replaced with
archaea. Consequently, incorporation of the mitochondrion - not
the origin of the nucleus - was hailed as the defining event in
eukaryotic origins. This opened the floodgates of speculation,
and numerous new hypotheses emerged. None is supported by
observation: no archaea reside within bacteria, no bacteria
reside within archaea, viruses have preposterously few
similarities to the nucleus, and no RNA cells exist.
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=