Download Diversity reigns in antibody responses

RESEARCH
IN S CIENCE JOURNAL S
Structure of the HIV-1
envelope protein
Lee et al., p. 1043
Edited by Nick Wigginton
ELECTRON TRANSPORT
Electrons that fow like a fuid
Electrons inside a conductor are often
described as fowing in response to an electric feld. This fow rarely resembles anything
like the familiar fow of water through a pipe,
but three groups describe counterexamples
(see the Perspective by Zaanen). Moll et al.
found that the viscosity of the electron fuid
in thin wires of PdCoO2 had a major efect
on the fow, much like what happens in
regular fuids. Bandurin et al. found evidence
in graphene of electron whirlpools similar
to those formed by viscous fuid fowing
through a small opening. Finally, Crossno
et al. observed a huge increase of thermal
transport in graphene, a signature of socalled Dirac fuids. — JS
Artistic rendering of Dirac fuid
experimentally observed in graphene
Science, this issue p. 1061, 1055, 1058; see also p. 1026
EBOLA VIRUS
IMMUNOLOGY
Resolving the
thermoelectric paradox
Profling the antibody
response to Ebola
Diversity reigns in
antibody responses
The existence of thermoelectric
efects in superconductors has
posed a particularly difcult
challenge for physicists. Not only
have experiments and theory
been in paradoxical discrepancy
by orders of magnitude, but
they often are in full disagreement with one another. Shelly
et al. resolved this stalemate
and developed an experimental
method using highly sensitive
quantum nanoscale interferometers. A theory that identifes
these thermoelectric efects in
superconductors supports the
experimental measurements.
This work may help lead to
practical applications of superconductors. — ZHK
During the course of an immune
response, B cells specifc for
an invading pathogen divide.
The antibodies they produce
increase in afnity via somatic
mutation in specialized lymph
node structures called germinal
centers. Tas et al. used multiphoton microscopy and sequencing
Sci. Adv. 2, 10.1126.
The recent Ebola virus outbreak in West Africa illustrates
the need not only for a vaccine
but for potential therapies,
too. One promising therapy is
monoclonal antibodies that
target Ebola’s membraneanchored glycoprotein (GP).
Bornholdt et al. isolated and
characterized 349 antibodies
from a survivor of the 2014 outbreak. A large fraction showed
some neutralizing activity
and several were quite potent.
Structural analysis revealed an
important site of vulnerability
on the membrane stalk region
of GP. Antibodies targeting this
area were therapeutically efective in Ebola virus–infected
mice. — KLM
sciadv.01250 (2016)
Science, this issue p. 1078
1038
to determine how diferent B
cell clones compete with one
another within mouse germinal
centers. Multiple B cell clones
can seed individual germinal
centers, and germinal centers
lose diversity at disparate rates.
Such heterogeneity suggests
that manipulating minor clonal
populations to gain an advantage during vaccination may
one day be possible. — KLM
Science, this issue p. 1048
Multiple B cell clones can make up a
single germinal center
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CREDITS: (TOP TO BOTTOM) SECOND BAY STUDIOS; TAS ET AL.
SUPERCONDUCTIVITY
GENE EXPRESSION
Doubling DNA
but not expression
As the genome replicates, and
before the cell divides, the copy
number of the replicated portions of the genome doubles.
In bacteria and archaea, gene
expression tracks with gene
dosage, both of which increase
after DNA replication. Voichek
et al., however, show that an
increase in DNA dosage after
replication does not increase
gene expression in budding
yeast. This expression bufering
is mediated by the acetylation
of newly synthesized histone
H3 deposited on the replicated
DNA. This acetylation helps
suppress transcription from the
excess DNA. — GR
Science, this issue p. 1087
CELL BIOLOGY
Separating dividing
cells into two
By activating genes involved in
cell growth and proliferation, the
transcriptional coactivator YAP
can act as a tumor promoter. Bui
et al. uncovered a nontranscriptional role for YAP in separating
dividing cells, a process called
cytokinesis. In mitotic cells,
YAP was localized to subcellular
structures that mediate cytokinesis, which ensured the proper
localization of other proteins
necessary for cytokinesis. Cells
defcient in YAP were more likely
to have an abnormal number of
chromosomes, a condition that
can give rise to tumors. — WW
PHOTO:© NATURE PICTURE LIBRARY/ALAMY STOCK PHOTO
Sci. Signal. 9, ra23 (2016).
CATALYSIS
Small olefns from syngas
The conversion of coal or natural
gas to liquid fuels or chemicals
often proceeds through the
production of CO and H2. This
mixture, known as syngas, is then
converted to hydrocarbons with
Fischer-Tropsch catalysts. For the
light olefns (ethylene to butylenes) needed for chemical and
polymer synthesis, conventional
catalysts are mechanistically
limited to <60% conversion
and deactivate through carbon
buildup. Jiao et al. developed a
bifunctional catalyst that achieves
higher conversions and avoids
deactivation (see the Perspective
by de Jong). A zinc-chromium
oxide creates ketene intermediates that are then coupled over a
zeolite. — PDS
IN OTHER JOURNALS
Edited by Sacha Vignieri
and Jesse Smith
Science, this issue p. 1065,
see also p. 1030
HUMAN ALTRUISM
Brain activity shows
underlying motives
In humans, two completely different motives may nevertheless
lead to exactly the same behavior. Because we can’t directly
observe motives, modern economists often completely disregard
them. However, Hein et al., using
fMRI, show that diferent human
motives can yield observable
responses in the brain (see
the Perspective by Gluth and
Fontanesi). In empathy-based
and reciprocity-based altruistic
behavior, the direction and the
strength of functional connectivity between specifc brain
regions were diferent for each
motive. Moreover, the connectivity patterns were independent
of the behavioral implications of
the motives. — PRS
Science, this issue p. 1074;
see also p. 1028
FLEXIBLE ELECTRONICS
Make it stretch,
make it glow
The skins of some cephalopods,
such as the octopus, are highly
fexible and contain color-changing cells. These cells are loaded
with pigments that enable rapid
and detailed camoufaging abilities. Larson et al. developed a
stretchable electroluminescent
actuator. The material could
be highly stretched, could emit
light, and could also sense
internal and external pressure.
A soft robot demonstrated
these combined capabilities by
stretching and emitting light as it
moved. — MSL
Science, this issue p. 1071
A common type of earthworm, Lumbricus terrestris
PLASTIC POLLUTION
Earthworms on a microplastics diet
M
icroplastics commonly found in marine environments
can cause harm to marine organisms when ingested.
Terrestrial environments are also widely polluted
with plastics, but little is known about their efect on
terrestrial species. Huerta Lwanga et al. have investigated the efect of polyethylene microplastics in plant litter
on earthworms. To provide a realistic exposure scenario, the
authors added the microplastics to plant litter deposited on
the soil surface. They show that environmentally relevant
microplastic concentrations led to reduced earthworm growth
and elevated mortality as compared to a control. Futhermore,
earthworms may transport microplastics into soils, from
which they may leach into surface waters. — JFU
Environ. Sci. Technol. 10.1021/acs.est.5b05478 (2016).
MICROBIOTA
For health, microbial
location matters
The composition of our gut
microbes probably afects our
health. For instance, certain
microbes may predispose individuals to some types of cancer,
alter their metabolism, or even
contribute to the aging process.
SCIENCE sciencemag.org
In fies, an altered microbial
composition in the gastrointestinal (GI) tract can reduce life
span. Li et al. investigated this
further and found that the GI
tract of younger fies compartmentalizes its resident microbes.
As fies age, however, infammatory signaling causes changes
in the cells lining the GI tract,
reducing its ability to maintain
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RESEARCH
ALSO IN SCIENCE JOURNALS
Edited by Nick Wigginton
STRUCTURAL BIOLOGY
FIBROSIS
DNA REPAIR
QUANTUM COMPUTING
A more complete look at
the HIV-1 envelope
SRC shows its stripes
To have or have not
determines DNA repair
Reducing quantum
overhead
Cells presumably try to protect
DNA from damage at all costs.
But Uphof et al. show that they
do not, because the cost is too
high. Single-molecule and singlecell measurements show that the
DNA repair enzyme Ada, which
also regulates its own expression,
was present in such low amounts
in E. coli that stochastic variation
led to some cells having none
of the protein at all. Such cells
undergo increased mutagenesis,
which could be benefcial in
circumstances in which increased
genetic heterogeneity is required
for adaptation. The expression
of large amounts of such a DNAaltering protein was also toxic.
— LBR
A quantum computer is
expected to outperform its
classical counterpart in certain
tasks. One such task is the
factorization of large integers,
the technology that underpins
the security of bank cards and
online privacy. Using a smallscale quantum computer
comprising fve trapped calcium
ions, Monz et al. implement
a scalable version of Shor’s
factorization algorithm. With the
function of ions being recycled
and the architecture scalable,
the process is more efcient
than previous implementations.
The approach thus provides the
potential for designing a powerful quantum computer, but with
fewer resources. — ISO
HIV-1 uses its envelope protein
(Env), a large glycoprotein present on the viral surface, to enter
target cells. Env forms trimers
on the viral surface. Structural
studies of solubilized Env
trimers have provided important insights into viral entry and
antibody binding, but soluble
trimers lack several important
insoluble regions of the native
protein. Lee et al. used cryo–
electron microscopy to solve
the structure of a trimeric Env
protein of HIV-1, missing only its
cytoplasmic tail, in complex with
broadly neutralizing antibodies.
A more complete understanding of Env’s structure may aid in
vaccine design eforts. — KLM
Science, this issue p. 1043
IMMUNOGENOMICS
Regulatory use of
endogenous retroviruses
Mammalian genomes contain
many endogenous retroviruses
(ERVs), which have a range of evolutionary ages. The propagation
and maintenance of these genetic
elements have been attributed to
their ability to contribute to gene
regulation. Chuong et al. demonstrate that some ERV families are
enriched in regulatory elements,
so that they act as independently
evolved enhancers for immune
genes in both humans and mice
(see the Perspective by Lynch).
The analysis revealed a primatespecifc element that orchestrates
the transcriptional response
to interferons. Selection can
therefore act on selfsh genetic
elements to generate novel gene
networks. — LMZ
Science, this issue p. 1083
see also p. 1029
The nonreceptor tyrosine kinase
SRC is a proto-oncogene that
has been associated with cancer
progression. Turro et al. found
a gain-of-function mutation
in SRC in nine patients with
myelofbrosis, bleeding, and
bone disorders. This mutation
prevented SRC from inhibiting
itself. The overactive enzyme
also enhanced tyrosine phosphorylation in a zebrafsh model
and in patient-derived cells. In
patients with myelofbrosis, this
SRC mutation was associated
with increased outgrowth of
myeloid and megakaryocytic
colonies and abnormal platelet
production, which could be
rescued by SRC kinase inhibition. These fndings provide a
possible explanation for the
severe bleeding seen in cancer
patients treated with inhibitors
of Src family kinases. — ACC
Sci. Transl. Med. 8, 328ra30 (2016).
NEURAL COMPUTATION
Credit assignment
in the brain
To discover relevant clues for
survival, an organism must bridge
the gap between the short time
periods when a clue occurs and
the potentially long waiting times
after which feedback arrives. This
so-called temporal credit-assignment problem is also a major
challenge in machine learning.
Gütig developed a representation of the responses of spiking
neurons, whose derivative defnes
the direction along which a
neuron’s response changes most
rapidly. By using a learning rule
that follows this development,
the temporal credit-assignment
problem can be solved by training
a neuron to match its number
of output spikes to the number
of clues. The same learning rule
endows unsupervised neural
networks with powerful learning
capabilities. — PRS
Science, this issue p. 1094
Science, this issue p. 1068
TRANSCRIPTION
Choosing where to
start transcription
The RNA polymerase enzyme
complex binds to the promoter
of a gene and separates the two
DNA strands. The subsequently
formed “transcription bubble”
is required for RNA synthesis
to begin. How RNA polymerase
chooses the exact DNA base at
which it will start transcription
has been unclear. Winkelman
et al. show that a control element upstream of the start
site is involved in helping RNA
polymerase make this choice
in bacteria. Start site selection
involves promoter scrunching,
where a stationary RNA polymerase unwinds and pulls DNA
through the active site, scrunching the DNA of the transcription
bubble. — GR
Science, this issue p. 1090
CANCER BIOLOGY
Have cancer stem cells
MET their match?
Solid tumors have been hypothesized to contain a subset of
highly aggressive cells that fuel
tumor growth and metastasis.
The search is on for drugs that
selectively kill or diminish the
malignant properties of these
tumor-initiating cells (TICs;
previously called “cancer stem
cells”). Pattabiraman et al.
hypothesized that compounds
that induce TICs to undergo a
phenotypic change called the
mesenchymal-to-epithelial
transition (MET) would therefore
cause TICs to lose their tumorinitiating ability. Indeed, drugs
activating the protein kinase
A signaling pathway triggered
an epigenetic reprogramming
of TICs that resulted in the
cells acquiring a more benign
epithelial-like phenotype. — PAK
Science, this issue p. 1042
Science, this issue p. 1041
1040-B
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