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Cell fate: Transition
loses its invasive edge
Two studies
provide evidence that epithelial tumour cells do not
need to transition to a mesenchymal-cell state to form
metastases, but that this process does contribute to
drug resistance.
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Ecology: Ecosystem
vulnerability to ocean warming
Analysis of the
temperature ranges occupied by marine species finds that
the vulnerability of ecological communities to global
warming may depend more on organismal physiology than on
the magnitude of change.
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Allosteric ligands for
the pharmacologically dark receptors GPR68 and
GPR65
Yeast-based
screening identifies the benzodiazepine drug lorazepam
as a non-selective positive allosteric modulator of the
G-protein-coupled receptor (GPCR) GPR68; homology
modelling and molecular docking of 3.1 million molecules
found a new compound, ‘ogerin’, as a potent GPR68
modulator, which suppressed recall in fear conditioning
in wild-type mice, and the general method of combining
physical and structure-based screening may lead to the
discovery of selective ligands for other
GPCRs.
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Dpp spreading is
required for medial but not for lateral wing disc
growth
The morphogen
Decapentaplegic (Dpp) has been implicated in both wing
patterning and growth in fruitflies; here, a
nanobody-based morphotrap approach has been developed
that rules out a role for the Dpp gradient in regulating
lateral wing growth.
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Epithelial-to-mesenchymal
transition is not required for lung metastasis but
contributes to chemoresistance
An
epithelial-to-mesenchymal transition (EMT)
lineage-tracing system in a mouse model of
breast-to-lung metastasis reveals that although some
cells undergo EMT in a primary epithelial tumour, the
lung metastases mainly arise from cells that have not
undergone EMT; in addition, cells that have undergone
EMT appear more resistant to
chemotherapy.
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Thermal biases and
vulnerability to warming in the world’s marine
fauna
How marine
communities will respond to climate change depends on
the thermal sensitivities of existing communities;
existing reef communities do not show a perfect fit
between current temperatures and the thermal niches of
the species within them and this thermal bias is a major
contributor to projected local species
loss.
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DNA-dependent
formation of transcription factor pairs alters their
binding specificity
A
high-throughput analysis of DNA binding in over 9,000
interacting transcription factor pairs reveals that the
interactions are often actively mediated by the DNA
itself and the composite DNA sites recognized are
different from the individual motifs of each
transcription factor.
|
Diversion of aspartate
in ASS1-deficient tumours fosters de novo
pyrimidine synthesis
ASS1, a urea
cycle enzyme, promotes cancer cell proliferation by
facilitating pyrimidine synthesis via CAD
(carbamoyl-phosphate synthase 2, aspartate
transcarbamylase, and dihydroorotase complex)
activation.
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Genetic predisposition
to neuroblastoma mediated by a LMO1
super-enhancer polymorphism
A causal variant
is identified at the LMO1 oncogene locus that
drives the genetic association of LMO1 with
neuroblastoma susceptibility; the causal SNP disrupts a
GATA transcription factor binding site within a
tissue-specific super-enhancer element in the first
intron of LMO1, thereby affecting LMO1
expression.
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Transcriptional
regulators form diverse groups with context-dependent
regulatory functions
A large-scale
enhancer complementation assay assessing the activating
or repressing contributions of over 800 Drosophila
transcription factors and cofactors to combinatorial
enhancer control reveals a more complex picture than
expected, with many factors having diverse regulatory
functions that depend on the enhancer
context.
|
Single-molecule
sequencing of the desiccation-tolerant grass
Oropetium thomaeum.
OPEN
Oropetium
thomaeum is a resurrection plant that can survive
extreme water stress through desiccation to complete
dryness, providing a model for drought tolerance; here,
whole-genome sequencing and assembly of the
Oropetium genome using single-molecule real-time
sequencing is reported.
|
Force generation by
skeletal muscle is controlled by mechanosensing in
myosin filaments
It is widely
accepted that contraction of skeletal muscle and the
heart involves structural changes in actin-containing
thin filaments to allow binding of myosin motors from
neighbouring thick filaments, thus driving filament
sliding; here, X-ray diffraction of single skeletal
muscle cells reveals that this thin-filament mechanism
can regulate muscle contraction against low load, but
high-load contraction requires a second permissive step
involving a structural change in the thick
filament.
|
Decapentaplegic and
growth control in the developing Drosophila
wing
The morphogen
Decapentaplegic (Dpp) has been implicated in both wing
patterning and growth in fruitflies; here, a CRISPR–Cas9
approach is used to rule out the Dpp gradient driving
wing growth.
|
Extra adsorption and
adsorbate superlattice formation in metal-organic
frameworks
Metal-organic
frameworks have a porous structure that has useful
applications in gas adsorption; here, small-angle X-ray
scattering is used to visualize the process of
adsorption as gas pressure increases, revealing that
adsorbate molecules interact across pore walls in a way
that allows extra adsorbate domains to be created in the
framework and to form superlattices, before the
adsorbate settles down into a more uniform
distribution.
|
Extremely metal-poor
stars from the cosmic dawn in the bulge of the Milky
Way
The first stars
and their immediate successors should be found today in
the central regions (bulges) of galaxies; old,
metal-poor stars have now been found in the Milky Way
bulge, including one star with an iron abundance about
10,000 times lower than that of the Sun without
noticeable carbon enhancement, making it possibly the
oldest known star in the Galaxy.
|
Epithelial-to-mesenchymal
transition is dispensable for metastasis but induces
chemoresistance in pancreatic cancer
Deletion of
Twist or Snail, two key transcription factors that
induce epithelial-to-mesenchymal transition in a mouse
model of pancreatic ductal adenocarcinoma leads to an
increase in cell proliferation, and a greater
sensitivity to the chemotherapeutic agent gemcitabine,
with no effect on invasion or
metastasis.
|
Corrigendum:
Regulatory analysis of the C. elegans genome with
spatiotemporal resolution
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Nature
Energy: Call for
Papers
Launching in January
2016, Nature Energy is now open for
submissions and inviting high-quality research
from across the natural and social sciences. The
journal will be dedicated to exploring all
aspects of the on-going discussion of energy
provision; from the generation and storage of
energy, to its distribution and management, the
needs and demands of the different actors, and
the impacts that energy technologies and
policies have on societies.
Submit your next research paper to
the journal.
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Basomedial amygdala
mediates top-down control of anxiety and fear
Activation of
the ventral medial prefrontal cortex–basomedial amygdala
pathway is shown to suppress anxiety and fear-related
freezing in mice, thus identifying the basomedial
amygdala (and not intercalated cells, as posited by
earlier models) as a novel target of top-down
control.
Avishek
Adhikari, Talia N. Lerner, Joel Finkelstein et
al. |
BCL11A enhancer
dissection by Cas9-mediated in situ saturating
mutagenesis
A CRISPR-Cas9
approach is used to perform saturating mutagenesis of
the human and mouse BCL11A enhancers, producing a
map that reveals critical regions and specific
vulnerabilities; BCL11A enhancer disruption is
validated by CRISPR-Cas9 as a therapeutic strategy for
inducing fetal haemoglobin by applying it in both mice
and primary human erythroblast cells.
Matthew
C. Canver, Elenoe C. Smith, Falak Sher et
al. |
Oxidative stress
inhibits distant metastasis by human melanoma
cells
Human melanoma
cells grown in mice experience high levels of oxidative
stress in the bloodstream such that few metastasizing
cells survive to form tumours; the rare melanoma cells
that successfully metastasize undergo metabolic changes
that increase their capacity to withstand this stress,
and antioxidant treatments increase metastasis formation
by human melanoma cells, while inhibiting antioxidant
pathways had the reverse effect.
Elena
Piskounova, Michalis Agathocleous, Malea M. Murphy
et al. |
Cryo-electron
microscopy structure of the Slo2.2
Na+-activated K+
channel
The structure of
the full-length Slo2.2 Na+-activated
K+ channel is determined by cryo-electron
microscopy, revealing features that explain the high
conductance and gating mechanism of the Slo
K+ channel family.
Richard
K. Hite, Peng Yuan, Zongli Li et al.
| |
Resensitizing
daclatasvir-resistant hepatitis C variants by allosteric
modulation of NS5A
The drug
daclatasvir (DCV), which inhibits the hepatitis C virus
(HCV) non-structural protein 5A (NS5A), can successfully
reduce viral load in patients; here, a combination of
DCV and an NS5A analogue is shown to enhance DCV potency
on multiple genotypes and overcome resistance in
vitro and in a mouse model.
Jin-Hua
Sun, Donald R. O’Boyle II, Robert A. Fridell et
al. |
Global non-linear
effect of temperature on economic production
Economic
productivity is shown to peak at an annual average
temperature of 13 °C and decline at high temperatures,
indicating that climate change is expected to lower
global incomes more than 20% by 2100.
Marshall
Burke, Solomon M. Hsiang, Edward Miguel |
A rocky planet
transiting a nearby low-mass star
A low-mass star
that is just 12 parsecs away from Earth is shown to be
transited by an Earth-sized planet, GJ 1132b, which
probably has a rock/iron composition and might support a
substantial atmosphere.
Zachory
K. Berta-Thompson, Jonathan Irwin, David Charbonneau
et al. |
Entangling two
transportable neutral atoms via local spin
exchange
Spin-entangled
states between two neutral atoms in different optical
tweezers are prepared by combining them in the same
optical tweezer and allowing for controlled
interactions, after which the particles are dynamically
separated in space and their entanglement is
maintained.
A.
M. Kaufman, B. J. Lester, M. Foss-Feig et
al. |
Large anomalous Hall
effect in a non-collinear antiferromagnet at room
temperature
The Hall effect
is sometimes encountered in ferromagnetic materials in
the absence of an external magnetic field; this
so-called anomalous Hall effect is now reported in the
antiferromagnetic material Mn3Sn, where it
occurs as a consequence of the unusual and complex
arrangement of the constituent magnetic
moments.
Satoru
Nakatsuji, Naoki Kiyohara, Tomoya Higo |
Liquids with permanent
porosity
Porous materials
find use in applications such as gas separation, drug
delivery and energy storage, but have hitherto been
solid rather than liquid; now a combination of cage
molecules and a crown-ether solvent that cannot enter
the cage molecules is used to create a porous liquid
that can solubilize methane gas better than non-porous
liquids.
Nicola
Giri, Mario G. Del Pópolo, Gavin Melaugh et
al. |
Plate tectonics on the
Earth triggered by plume-induced subduction
initiation
High-resolution
three-dimensional thermomechanical simulations of
Earth's lithosphere indicate that mantle plumes could
have initiated the first subduction zones, but only in
the hotter early Earth for old oceanic
plates.
T.
V. Gerya, R. J. Stern, M. Baes et al.
|
Widespread
exploitation of the honeybee by early Neolithic
farmers
Detection of
molecular biomarkers characteristic of beeswax in
pottery vessels at archaeological sites reveals that
humans have exploited bee products (such as beeswax and
honey) at least 9,000 years ago since the beginnings of
agriculture.
Mélanie
Roffet-Salque, Martine Regert, Richard P. Evershed
et al. |
Deep-time evolution of
regeneration and preaxial polarity in tetrapod limb
development
Salamanders are
the only tetrapod that can fully regenerate their limbs
and tail, a capacity that might be linked to their
unique preaxial mode of limb development; here, data
from fossils reveal the existence of preaxial polarity
in various amphibians from the Carboniferous and Permian
periods, suggesting that salamander-like regeneration is
an ancient feature of tetrapods that was subsequently
lost at least once in the lineage leading to
amniotes.
Nadia
B. Fröbisch, Constanze Bickelmann, Jennifer C. Olori
et al. |
Oxygen regulation of
breathing through an olfactory receptor activated by
lactate
In addition to
its role in olfaction, Olfr78 is involved in sensing
hypoxia.
Andy
J. Chang, Fabian E. Ortega, Johannes Riegler et
al. |
Epigenetic silencing
of TH1-type chemokines shapes tumour immunity
and immunotherapy
Treating ovarian
cancer in mouse models with inhibitors for the
epigenetic regulators EZH2 and DNMT1 increases the
expression of the inflammatory chemokines CXCL9 and
CXCL10, resulting in enhanced tumour infiltration by
effector T cells, and slowed tumour
progression.
Dongjun
Peng, Ilona Kryczek, Nisha Nagarsheth et
al. |
The DNA glycosylase
AlkD uses a non-base-flipping mechanism to excise bulky
lesions
Crystal
structures of the DNA glycosylase AlkD with DNA
containing various modified bases show that neither
substrate recognition nor catalysis use a base-flipping
mechanism; instead, AlkD scans the phosphodeoxyribose
backbone for increased cationic charge imparted by the
alkylated base, and then uses the positive charge to
facilitate cleavage of the glycosidic bond, thus
explaining the specificity of AlkD for cationic
lesions.
Elwood
A. Mullins, Rongxin Shi, Zachary D. Parsons et
al. |
Structure of a
eukaryotic SWEET transporter in a homotrimeric
complex
The X-ray
crystal structure is presented of a seven-transmembrane
eukaryotic SWEET glucose transporter, revealing the link
between seven-transmembrane eukaryotic SWEETs and their
three-transmembrane bacterial homologues and providing
insight into eukaryotic sugar transport
mechanisms.
Yuyong
Tao, Lily S. Cheung, Shuo Li et al.
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