ScienceWeek July 28, 2007
Dan Agin
July 28, 2007
Vol. 11 - Number 29
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I thank God I was not made a dextrous manipulator; the most
important of my discoveries have been suggested to me by my
failures.
-- Humphry Davy (1778-1829)
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Contents (full text below):
1. Paleontology: Variation and Early Evolution
2. Materials Science: Filling a Void
3. Physics: Pierre-Gilles de Gennes (1932-2007)
4. Book Review: Psychology: The Nature of Belief
5. Astrobiology: Photosynthesis in Watercolours
6. Developmental Biology: A Ten Per Cent Solution
7. Inflammatory Disease: Assault on the Guardian
8. Obituary: Horst Tobias Witt (1922-2007)
9. Unravelling the Pathogenesis of Inflammatory Bowel Disease
10. The Spread of Obesity in a Large Social Network over 32 Years
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1.
Science 27 July 2007: Vol. 317. no. 5837, pp. 459 - 460 DOI:
10.1126/science.1145550
Paleontology: Variation and Early Evolution
Gene Hunt
Variation is often said to be the raw material for evolution. In
the absence of heritable variation, no mechanism--natural
selection included--can cause evolutionary change within
populations. That variation is necessary for evolution is
uncontroversial, but scientists have long wondered if abundant
variation might play a more active role in facilitating or
channeling evolutionary change (1, 2). Any evolutionary influence
of variation would presumably operate continually, but there have
been some indications that during the Early Cambrian (542 to 513
million years ago), the link between variation and evolutionary
divergence may have been especially strong.
At roughly the same time as the greatest known burst of
biological innovation, the Cambrian Explosion of animal body
plans, it appears that species may have been unusually variable
in their morphology. Although intriguing, the evidence for this
increased Cambrian variability has been somewhat equivocal.
However, on page 499 of this issue, Webster (3) presents the
results of a novel analysis of trilobite variability that puts
this pattern on much firmer empirical footing. He reports that
during the heyday of innovation in the Cambrian, trilobite
species were in fact unusually variable, more so than at any
other time in their history.
Previous suggestions of elevated Cambrian variability involve a
variety of taxa, but special emphasis has been placed on
trilobites (4, 5), which have by far the richest fossil record
during this interval. One commonly cited example is the number of
body segments in the thorax of adult trilobites. Within some
Cambrian species, this feature is variable, whereas in post-
Cambrian trilobites, the number of segments is almost always
fixed within species, and often within higher taxonomic levels
such as genera and families (6). As interesting as this example
is, it applies to only one trait and a small number of trilobite
species. More convincing evidence for enhanced variation would
require a broader and more systematic survey of characters and
traits, but there are formidable obstacles to measuring variation
in a meaningful way across very different traits and taxa.
Webster gets around these difficulties by cleverly exploiting a
large set of expert observations already in existence. Since the
advent of cladistic methods in systematics, specialists generally
represent their morphological observations as explicitly defined
characters with discretely coded character states. For example, a
character might reflect the number of ridges in a defined region
of the trilobite head, and there would be different character
states corresponding to the presence of one ridge, two ridges,
and so on. Systematists not only record the character state
attributed to each species in a study but also usually indicate
for each character which species were variable. Such coding of
species represented by individuals with two or more different
character states is called "polymorphic" by systematists.
By tracking the preponderance of polymorphic versus invariant
characters over time, Webster was able to document a dramatic
pattern: In the early intervals of trilobite evolution (the Early
and Middle Cambrian), polymorphism was much more common than in
any subsequent period of trilobite history. Because the elevated
polymorphism was not limited to any particular kinds of traits,
trilobite species during these early intervals were very likely
to have been exceptionally variable in their overall morphology.
Moreover, this period of elevated polymorphism occurs at the same
time that trilobites were diversifying taxonomically and
morphologically, suggesting to Webster that elevated variation
may have promoted the radiation of trilobites. Although this
large data set of observations is not a random sample of
trilobite lineages or traits, a variety of sensitivity analyses
suggest that whatever its biases, they do not appear to change
markedly over time.
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2.
Science 27 July 2007: Vol. 317. no. 5837, pp. 460 - 461 DOI:
10.1126/science.1146517
Materials Science: Filling a Void
Stephanie L. Brock
Porous inorganic materials are widely used as filters and
catalysts--applications that involve the transport of molecules
or ions to reactive surfaces. Such materials include zeolites and
mesoporous solids (both of which have ordered pore structures),
as well as dried gel structures such as aerogels (with a
disordered pore structure). The materials vary in the number,
size, and distribution of pores, but with few exceptions, they
are oxides. This "chemical exclusivity" has severely limited
their potential applications. Thus, zeolites efficiently absorb
calcium and magnesium ions and are therefore effective water-
softening agents, but they are largely ineffective for
remediation of heavy metal ions, such as mercury or lead.
The problem with oxides is that they prefer to form bonds with
small metal ions such as magnesium and zinc. Heavy metals are
large and polarizable and cannot be effectively bound by porous
oxides. One way to get around this problem involves modifying the
surface of the oxide so that it presents a larger, more
polarizable binding atom, such as a sulfur group, permitting
selective adsorption of heavy metal ions (1). On page 490 of this
issue, Bag et al. report another approach (2): They use a sol-gel
reaction to construct porous solids that are analogous to oxides
but contain the heavier chalcogenides (such as sulfides or
selenides) instead of oxide. The resulting chalcogenide aerogels
selectively bind heavy metals without requiring modification.
A few methods for making porous chalcogenide aerogels have
previously been reported. These methods used either thiolysis
chemistry, in which molecular metal precursors are reacted with
hydrogen sulfide (3), or the oxidative condensation of preformed
metal chalcogenide nanoparticles (4). The method reported by Bag
et al. promises additional flexibility because it starts from
molecular ions or small clusters of semiconducting metal
chalcogenides and uses metal ions as linkers. Both the cluster
and the metal ion can be varied to adjust the properties of the
resulting material.
This general approach--the linking of chalcogenido clusters with
metal ions--has been previously used to prepare mesostructured
chalcogenides (5-8). In these studies, surfactants served as
templates, organizing the metal chalcogenide component around the
micellar structures, analogous to the synthesis of mesoporous
aluminosilicate materials (9). However, in contrast to mesoporous
aluminosilicates, attempts to remove the surfactant by washing or
heating resulted in collapse of the pore structure. The present
surfactant-free strategy is simpler, eschewing order completely,
yet generating stable porous structures.
Bag et al. use a metathesis (or partner-switching) reaction
between a metal chalcogenide salt and tetrachloroplatinate in
aqueous solution to obtain a solvent-swollen chalcogenide
polymer. Wringing out this "sponge" without collapsing the
structure can be achieved by drying from a supercritical solvent,
producing an aerogel [a term that refers to the fact that the
pore solvent has been replaced by air (10)].
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3.
Science 27 July 2007: Vol. 317. no. 5837, p. 466 DOI:
10.1126/science.1146688
Physics: Pierre-Gilles de Gennes (1932-2007)
Armand Ajdari
Described as the "Isaac Newton of our time" by the Royal Swedish
Academy in the citation for his Nobel Prize in Physics in 1991,
Pierre-Gilles de Gennes died on 18 May 2007 at the age of 74.
Beyond the remarkable lecturer and the advocate of science and
scientific research cherished by media and students, Pierre-
Gilles de Gennes was above all one of the greatest physicists of
the 20th century. The depth and breadth of his scientific
achievements are exceptional. In the last year of his life, de
Gennes published articles in five different areas, from the
motion of dislocations in the quantum regime to the storage of
olfactory information in the brain.
De Gennes was born in 1932 to a family of medical doctors. He
began his academic career at the Ecole Normale Supérieure in
Paris, followed by 4 years at the Commissariat à l'Energie
Atomique in Saclay. In his early work, he focused on magnetism,
studying the scattering of neutrons in metallic materials close
to magnetic transitions, as well as questions regarding spin
waves and rare earths. A postdoctoral stay at Berkeley in the
group of Charles Kittel followed, before a 2-year stint in the
French Navy.
Moving to Orsay in 1961, de Gennes founded an experimental and
theoretical effort on superconductors. His work led to important
insights into surface superconductivity and into
superconductivity without band-gap. Around 1968, de Gennes began
to revisit the field of liquid crystals, drawing fruitful formal
analogies with superconductors. His insights had a substantial
impact on the physical understanding of these materials, which
now play an important part in many technologies such as liquid
crystal displays.
In 1971, de Gennes was appointed professor at the Collège de
France. He then shifted his interest to polymers and to other
topics previously categorized as chemistry. Drawing on his
creativity, his genius at simplifying problems, and his ability
to establish connections with sophisticated formal theories of
statistical physics, he demonstrated the power of physics in
dealing with these systems. This field is today called soft
condensed- matter physics. As he had done previously, de Gennes
teamed up with experimentalists at the Collège de France, in
Saclay, and in Strasbourg to stimulate his creativity and
validate his predictions.
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4.
Science 27 July 2007: Vol. 317. no. 5837, p. 456 DOI:
10.1126/science.1142653
Book Review: Psychology: The Nature of Belief
Reviewed by Scott Atran
Six Impossible Things Before Breakfast: The Evolutionary Origins
of Belief
by Lewis Wolpert. Faber and Faber, London, 2006. 243 pp., £14.99.
ISBN 9780571209200. Norton, New York, 2007. 255 pp. $25.95. ISBN
9780393064490.
In explaining why he wrote Six Impossible Things Before
Breakfast, Lewis Wolpert describes a disturbing encounter with
his son's envious belief that father has the advantage in life
because he is likely to die sooner and enjoy heaven. In August
2005, while with Muslim mujahedin in Sulawesi, I noticed tears
welling up in my traveling companion, Farkhin (who helped bomb
the Philippine ambassador's residence in Jakarta and had hosted
9/11 mastermind Khalid Sheikh Mohammed) when he heard of a young
man killed in a skirmish with Christian fighters. "Farkhin, you
knew the boy?" I asked. "No," he lamented, "but he was only in
the Jihad a few weeks; I've been fighting since Afghanistan [late
1980s] and I'm still not a martyr."
In trying to grasp his son's belief as well as the beliefs of
people like suicide bombers and today's great clashes among
religious and political beliefs, Wolpert draws fresh insight from
the biological and evolutionary roots of belief. He surveys a
vast domain that begins with children's innate ideas about the
differences between how inert objects and animate agents like
people interact and ends with the almost miraculous breakaway of
scientific beliefs from our intuitive understanding of the world:
there are more molecules in a glass of water than glasses of
water in the oceans. We find out that other primates lack mental
equipment for mind reading. They can't represent or embed
another's beliefs in their own thoughts ("John believes that Mary
thinks that..."). Thus they can't understand how they or others can
have false beliefs or conceive of fiction, God, or scientific
truth. And we learn why other animals can't truly imitate or
learn a new dance and why homeopathic medicine and psychotherapy
involve "beliefs related to witchcraft."
The book's unifying theme is that all belief is ultimately rooted
in causal understanding and has its evolutionary origins in the
use and manufacture of tools. This lets Wolpert scan the
landscape of belief with clarity and direction but leads down the
wrong path in key areas. He argues that managing fire "might have
been one of the origins of market exchange, and might have led to
the advantage of humans knowing about numbers." Yet defining
aspects of number, such as the concept of a class of similar
classes or of infinite discreteness, relate more to
categorization processes and language structure than to
causality. We are told "Verbs ranging from 'go' to 'hit' to
'throw' require causal thinking ... an essential prerequisite for
language development." Now Kanzi, a brilliant bonobo, can use
symbolic tokens to reference causal relations between actions and
goals; however, Kanzi's strings are usually action-action
combinations, such as "chase bite." These strings employ two
"predicates" and no subject. No human language allows sentences
that have no syntactic arguments and thus cannot express a
subject-predicate proposition. Hominid tool play tells us little
of testable, scientific interest about linguistic structure,
number, or markets.
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5.
Nature 448, 418 (26 July 2007) | doi:10.1038/448418a; Published
online 25 July 2007
Astrobiology: Photosynthesis in Watercolours
John Raven
The spectrum of stellar radiation available to an organism is
altered by the atmosphere and water on the planet it inhabits.
Study of this relationship can outline the limits to
photosynthesis.
Water is essential for life 'as we know it', and the search for
life 'as we don't know it' elsewhere in the Universe centres on
the search for evidence of water1. But the properties of water
that make it essential for organisms and their environments can
also restrict organisms' activities. An example that has now been
re-investigated by Kiang et al.2, 3 and by Stomp et al.4 is the
wavelength dependence of the absorption of electromagnetic
radiation by water, and also by permanent atmospheric gases. Such
studies can inform our understanding of the distribution and
pigmentation of photosynthetic organisms on Earth2, 3, 4, and on
any life-supporting Earth-like planets in other solar systems.
This biological dark side of water - its absorption of solar
electromagnetic radiation - creates habitats that restrict or
eliminate the roles of solar radiation in supplying energy for
photosynthesis and information to sensory systems. The effective
absence of solar radiation deep in large bodies of water such as
lakes and oceans has long been recognized, and limits
photosynthesis with this energy source to at most the top few
hundred metres of water bodies, and to the land surface. The
significance of water's wavelength-dependent attenuation of solar
radiation for photosynthesis by aquatic organisms has been
recognized since the late nineteenth century. Engelmann5, with
his theory of complementary chromatic adaptation, suggested in
1883 that the depth at which seaweeds with different pigments
grow might be related to the spectrum of incident radiation they
receive.
Later work showed that Engelmann had underestimated the role of
dissolved and suspended material in modifying the radiation
attenuation due to water alone, and that, even when this was
taken into account, the quantitative significance of
complementary chromatic adaptation of seaweeds in nature was
small6. But Engelmann's perception was a great stimulus to study
of the photosynthetic pigmentation and the radiation environment
of organisms in relation to the absorption of radiation by water.
That work has extended to anoxygenic organisms (photosynthetic
bacteria)2, 3, 4 - that is, those whose photosynthesis does not
generate oxygen - as well as being carried out on the oxygenic
organisms considered by Engelmann, and also to other planets that
might support life4. On Earth, the advent of anoxygenic organisms
preceded that of oxygenic ones.
Kiang et al.2 surveyed the diversity of photosynthetic organisms,
and propose constraints on the evolution of the pigments that
harvest and transform radiation. One is the wavelength of the
peak photon flux in the environment. Another is the longest
wavelength that has sufficient energy per photon to bring about
the appropriate photochemical reaction (in which photon energy is
converted into chemical energy). Organisms that produce oxygen
from water, a very energy-intensive reaction, are constrained to
using shorter wavelengths than are those that do not produce
oxygen. This is the case despite the oxygen producers using two
photochemical reactions in series, rather than a single reaction,
as seen in anoxygenic organisms. The sorts of photochemistry that
can occur, and the pigmentation of the organisms, are greatly
influenced by the absorption of solar radiation by water (and
oxygen) in the atmosphere and, for aquatic organisms, in the
water body in which they live2.
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6.
Nature 448, 420-421 (26 July 2007) | doi:10.1038/448420a;
Published online 25 July 2007
Developmental Biology: A Ten Per Cent Solution
John Reinitz
In early embryos, a concentration gradient of the Bicoid protein
affects pattern formation. Studies of living embryos reveal a
surprising level of accuracy in the Bicoid gradient. But is it
accurate enough?
A central idea in developmental biology is Lewis Wolpert's theory
of positional information1. This states that a substance present
in a concentration gradient induces different developmental fates
in cells when present at different concentrations. The first such
morphogenetic gradient to be identified was that of the gene
transcription factor Bicoid in embryos of the fruitfly Drosophila
melanogaster2, 3. This protein is distributed with an exponential
profile, with its concentration decreasing towards the posterior
pole of the embryo. Although the importance of the Bicoid
gradient in specifying cellular fates was established,
quantitative puzzles remained. These problems have now been
largely solved by Gregor and colleagues4, 5 in two papers in
Cell.
A previous study6 had shown that the Bicoid concentration
gradient varied far more widely between embryos than did the
expression of the hunchback (hb) gene, which is used as a readout
of the effect of Bicoid concentration. This and other studies,
however, were performed in fixed tissue, where it is impossible
to determine absolute protein concentrations or to follow changes
in gene expression over time.
Gregor et al.4 tagged Bicoid with enhanced green fluorescent
protein (eGFP), which allowed them to directly observe its
gradient in live embryos. For this, the authors constructed a
genetic line of fruitflies in which the bicoid gene (bcd) was
replaced by a functional bcd-egfp fusion gene. They then
monitored the gene's protein product by time-lapse microscopy
during the blastoderm stage of early embryonic development.
In early Drosophila development, the embryo is a syncytium - it
consists of a mass of cytoplasm, with nuclei that are not
separated by cell membranes. The nuclei undergo a series of 13
rapid divisions, with the blastoderm forming at about division
10. The authors found that it is at division 9 - before
blastoderm formation - that Bicoid-eGFP is first detected. As it
is a DNA-binding protein, Bicoid is localized in the nucleus. But
as nuclei lose their envelopes during each division, internally
stored Bicoid is released into the cytoplasm.
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7.
Nature 448, 421-422 (26 July 2007) | doi:10.1038/448421a;
Published online 25 July 2007
Inflammatory Disease: Assault on the Guardian
Richard M. Ransohoff
In multiple sclerosis, the immune system attacks 'self' tissues.
Ten years after the discovery of one target of this autoimmunity,
work with mice identifies it as a guardian protein produced in
response to inflammation.
On page 474 of this issue, Ousman and her co-workers1 describe
how autoimmunity to a protein known as alphaB-crystallin (CRYAB)
can contribute to inflammatory injury of the central nervous
system. They show that autoimmune attack on CRYAB does not
directly cause tissue damage. Rather, it worsens the severity of
damage by simultaneously eliminating two of the protein's
functions - its action as a restraining element for inflammation,
and its ability to inhibit programmed cell death of glial cells
in the nervous system.
The clinical context for this research is multiple sclerosis
(MS), an inflammatory disorder of the human central nervous
system. This disease selectively targets myelin, the complex,
lipid-rich membrane that enwraps some nerve axons. Its connection
with CRYAB began with an experiment that challenged orthodoxy: in
1995, van Noort et al.2 reported CRYAB to be a predominant target
of autoimmunity in MS. They discovered CRYAB's significance by
isolating myelin proteins from MS autopsy material, and
determining these proteins' ability to act as autoantigens in
evoking a reaction from T cells. These are major players in the
immune system, and both produce and are stimulated by cytokine
messenger molecules.
The group's finding2 came as a surprise. During many years of
research on autoimmune models of MS (known collectively as
experimental autoimmune encephalomyelitis, or EAE), investigators
had identified several myelin proteins with encephalitogenic
potential. Encephalitogenicity implies that immunization with the
protein, or with a peptide derived from it, could elicit an
autoimmune reaction, characterized by inflammation, demyelination
and weakness of the limbs. Known encephalitogenic agents
includedthe principal proteins of myelin - myelin basic protein
and myelin proteolipid protein - as well as minor components,
such as myelin oligodendroglial glycoprotein (MOG).
Van Noort and colleagues took the road "less traveled by" and
focused on myelin from patients with MS. Previously, the usual
assumption had been that any autoantigen present in myelin would
be a constituent of the healthy tissue. CRYAB was distinctly an
outlier, because it is expressed only at low levels in myelin
derived from the non-diseased central nervous system3. It belongs
to the family of small heat-shock proteins that are produced by
all cells in response to stress. CRYAB is also an oddity among
heat-shock proteins, however, being expressed selectively in the
eye lens, in skeletal and cardiac muscle, and in glial cells,
including oligodendrocytes (the cells that produce myelin) and
astrocytes.
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8.
Nature 448, 425 (26 July 2007) | doi:10.1038/448425a; Published
online 25 July 2007
Obituary: Horst Tobias Witt (1922-2007)
Wolfgang Junge1 & A. William Rutherford
During the second half of the twentieth century, great strides
were made in revealing the molecular details of oxygen-generating
photosynthesis, the basis of almost all life on Earth. Horst Witt
was one of the prime movers behind this revolution in
understanding.
Witt was born in 1922 in Bremen, Germany. From his youth he was
interested in physics, and while at school he won a prestigious
prize for his high-risk, and literally explosive, experiments on
supersonic airfoils. On the outbreak of the Second World War, he
entered the Luftwaffe, but his scientific aptitude led to his
early (and lucky) release to take up research at the University
of Göttingen. He received his PhD in solid-state physics in 1950,
and then moved to the Max Planck Institute of Physical Chemistry
where - like several other brilliant young scientists, including
Manfred Eigen - he began to explore the largely hidden beauties
of the molecular life sciences.
Witt chose oxygenic photosynthesis as his lifelong research
topic. Inspired by the methods pioneered by George Porter and
Ronald Norrish, he embarked on work with the technique of flash
spectrophotometry. Using algae, in 1955 he discovered reactions
of chlorophylls, carotenoids and cytochromes that occurred in
microseconds. By 1961, his work, along with the independent
discoveries of Lou Duysens and of Bessel Kok, led to a scheme
with two photochemical reaction centres in series. At photosystem
II, electrons are removed from water, generating a strong
oxidant, oxygen. At photosystem I, the electrons are used to
produce a strong reductant, NADPH (and thence sugars). The energy
difference between the strong oxidant and the strong reductant
powers all oxygen-based life.
At that time the two Nobel laureates in the field, biochemist
Otto Warburg and spectroscopist James Frank, were fighting their
famous battles from ensconced positions. When confronted with
Witt's detailed reaction scheme in 1962, Warburg mused: "Could
you tell us how the chemical mechanism of photosynthesis can be
described on the basis of your spectroscopic observations?" Witt
countered with a well-aimed jibe at his eminent critic, the
pioneer of oxygen detection, by observing that "it would be
difficult to deduce the mechanism of a combustion engine based
only on sniffing the exhaust".
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9.
Nature 448, 427-434 (26 July 2007) | doi:10.1038/nature06005
Unravelling the Pathogenesis of Inflammatory Bowel Disease
R. J. Xavier & D. K. Podolsky
Recently, substantial advances in the understanding of the
molecular pathogenesis of inflammatory bowel disease (IBD) have
been made owing to three related lines of investigation. First,
IBD has been found to be the most tractable of complex disorders
for discovering susceptibility genes, and these have shown the
importance of epithelial barrier function, and innate and
adaptive immunity in disease pathogenesis. Second, efforts
directed towards the identification of environmental factors
implicate commensal bacteria (or their products), rather than
conventional pathogens, as drivers of dysregulated immunity and
IBD. Third, murine models, which exhibit many of the features of
ulcerative colitis and seem to be bacteria-driven, have helped
unravel the pathogenesis/mucosal immunopathology of IBD.
The major forms of idiopathic IBD, ulcerative colitis and Crohn's
disease are chronic inflammatory disorders of the
gastrointestinal tract that have been empirically defined by
clinical, pathological, endoscopic and radiological features1.
The onset of IBD typically occurs in the second and third decades
of life and a majority of affected individuals progress to
relapsing and chronic disease. Family aggregation has long been
recognized. First-degree relatives of affected individuals have a
relative risk of fivefold or greater. The inheritable component
seems stronger in Crohn's disease than in ulcerative colitis2, 3.
It is of interest that in several countries with historically low
rates of IBD, a pattern of rising incidence in the past one to
two decades, particularly for Crohn's disease, has occurred,
suggesting that environmental factors are also involved.
Key features of ulcerative colitis include diffuse mucosal
inflammation that extends proximally from the rectum to a varying
degree. In conjunction with severe inflammation and the
coincident production of a complex mixture of inflammatory
mediators, extensive superficial mucosal ulceration develops.
Histopathological features include the presence of a significant
number of neutrophils within the lamina propria and the crypts,
where they form micro-abscesses (Fig. 1). Depletion of goblet
cell mucin is also common. Crohn's disease is characterized by
aggregation of macrophages that frequently form non-caseating
granulomas (Fig. 1). Although any site of the gastrointestinal
tract may be affected, involvement of the terminal ileum is most
common and the earliest mucosal lesions in Crohn's disease often
appear over Peyer's patches. Unlike ulcerative colitis, Crohn's
disease may be patchy and segmental, and inflammation typically
transmural.
Genome-wide searches for IBD susceptibility loci performed in the
last few years have been highly successful in identifying genes
that contribute to disease susceptibility. In initial screening
efforts, two groups identified NOD2 (also designated CARD15 and
IBD1) as a susceptibility gene in Crohn's disease, using
positional cloning and candidate gene approaches4, 5. Since then,
several additional susceptibility loci have been implicated in
inflammatory bowel disease and confirmed by replication: IBD5,
IL23R and ATG16L1 (refs 6, 7, 8, 9, 10, 11, 12, 13, 14). (See
Fig. 2 for the full list of genes validated in multiple studies
as well as those genes that require additional confirmation). The
genetic variants that have been found to confer Crohn's disease
risk point to the importance of innate immunity, autophagy and
phagocytosis in Crohn's disease pathogenesis. In particular, a
number of genes associated with Crohn's disease (IL23R, PTPN2)
are also associated with other autoimmune disorders, suggesting
that a subset of Crohn's disease patients share common triggers
with these conditions. In addition, multiple disease-associated
intergenic segments have been identified and replicated in
genome-wide association studies. These intergenic regions
implicate new genes and pathways-possibly including genes that
are expressed within these regions and others that are remotely
regulated to modify the disease phenotype. Further understanding
of regulatory elements within non-coding genomic regions and
gene-gene interactions will lead to a better understanding of the
underlying mechanisms that cause disease. Despite early linkage
analysis suggesting an important contribution of the MHC complex
to IBD susceptibility, in contrast to rheumatoid arthritis and
multiple sclerosis, identification of precise genes within the
MHC region that confer susceptibility has been problematic.
Individual risk genes are discussed below within the context of a
consideration of pathophysiologic mechanisms.
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10.
New England Journal of Medicine. Volume 357:370-379, July 26,
2007, Number 4.
The Spread of Obesity in a Large Social Network over 32 Years
Nicholas A. Christakis, M.D., Ph.D., M.P.H., and James H. Fowler,
Ph.D.
Background: The prevalence of obesity has increased substantially
over the past 30 years. We performed a quantitative analysis of
the nature and extent of the person-to-person spread of obesity
as a possible factor contributing to the obesity epidemic.
Methods: We evaluated a densely interconnected social network of
12,067 people assessed repeatedly from 1971 to 2003 as part of
the Framingham Heart Study. The body-mass index was available for
all subjects. We used longitudinal statistical models to examine
whether weight gain in one person was associated with weight gain
in his or her friends, siblings, spouse, and neighbors.
Results: Discernible clusters of obese persons (body-mass index
[the weight in kilograms divided by the square of the height in
meters], ?30) were present in the network at all time points, and
the clusters extended to three degrees of separation. These
clusters did not appear to be solely attributable to the
selective formation of social ties among obese persons. A
person's chances of becoming obese increased by 57% (95%
confidence interval [CI], 6 to 123) if he or she had a friend who
became obese in a given interval. Among pairs of adult siblings,
if one sibling became obese, the chance that the other would
become obese increased by 40% (95% CI, 21 to 60). If one spouse
became obese, the likelihood that the other spouse would become
obese increased by 37% (95% CI, 7 to 73). These effects were not
seen among neighbors in the immediate geographic location.
Persons of the same sex had relatively greater influence on each
other than those of the opposite sex. The spread of smoking
cessation did not account for the spread of obesity in the
network.
Conclusions: Network phenomena appear to be relevant to the
biologic and behavioral trait of obesity, and obesity appears to
spread through social ties. These findings have implications for
clinical and public health interventions.
The prevalence of obesity has increased from 23% to 31% over the
recent past in the United States, and 66% of adults are
overweight.1,2 Proposed explanations for the obesity epidemic
include societal changes that promote both inactivity and food
consumption.3 The fact that the increase in obesity during this
period cannot be explained by genetics4,5 and has occurred among
all socioeconomic groups1 provides support for a broad set of
social and environmental explanations. Since diverse phenomena
can spread within social networks,6,7,8,9,10 we conducted a study
to determine whether obesity might also spread from person to
person, possibly contributing to the epidemic, and if so, how the
spread might occur.
Whereas obesity has been stigmatized in the past, attitudes may
be changing.11,12 To the extent that obesity is a product of
voluntary choices or behaviors, the fact that people are embedded
in social networks and are influenced by the evident appearance
and behaviors of those around them suggests that weight gain in
one person might influence weight gain in others. Having obese
social contacts might change a person's tolerance for being obese
or might influence his or her adoption of specific behaviors
(e.g., smoking, eating, and exercising). In addition to such
strictly social mechanisms, it is plausible that physiological
imitation might occur; areas of the brain that correspond to
actions such as eating food may be stimulated if these actions
are observed in others.13 Even infectious causes of obesity are
conceivable.14,15
We evaluated a network of 12,067 people who underwent repeated
measurements over a period of 32 years. We examined several
aspects of the spread of obesity, including the existence of
clusters of obese persons within the network, the association
between one person's weight gain and weight gain among his or her
social contacts, the dependence of this association on the nature
of the social ties (e.g., ties between friends of different
kinds, siblings, spouses, and neighbors), and the influence of
sex, smoking behavior, and geographic distance between the
domiciles of persons in the social network.
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