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Cancer: Organ-seeking
vesicles
An analysis
reveals that cancer cells remotely prepare distant sites
for tumour spread in an organ-specific manner, by
deploying organ-seeking extracellular
vesicles.
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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.
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Fungal pathogen uses
sex pheromone receptor for chemotropic sensing of host
plant signals
Fungal pathogens
reorient hyphal growth towards their plant hosts in
response to chemical signals; here, directed growth of
the plant pathogen Fusarium oxysporum towards the
roots of the tomato plant is shown to be triggered by
class III peroxidases secreted by the tomato plant, with
the fungal response requiring a sex pheromone
receptor.
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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.
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Crystal structure of
the RNA-dependent RNA polymerase from influenza C
virus
The X-ray
crystal structure of influenza C virus polymerase,
captured in a closed, pre-activation confirmation, is
solved at 3.9 Å resolution; comparison with previous
RNA-bound structures reveals large conformational
changes associated with RNA binding and activation, and
illustrates the notable flexibility of the influenza
virus RNA polymerase.
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Autophagy mediates
degradation of nuclear lamina
In response to
cancer-associated stress, autophagy machinery mediates
degradation of nuclear lamina components in mammals,
suggesting that cells might degrade nuclear components
to prevent tumorigenesis.
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Methane storage in
flexible metal–organic frameworks with intrinsic thermal
management
Two flexible
metal-organic frameworks are presented as solid
adsorbents for methane that undergo reversible phase
transitions at specific methane pressures, enabling
greater storage capacities of usable methane than have
been achieved previously, while also providing internal
heat management of the system.
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In situ
structures of the segmented genome and RNA polymerase
complex inside a dsRNA virus
This study
visualizes the interior of a dsRNA virus using
cryo-electron microscopy, revealing the organization of
the genome of cytoplasmic polyhedrosis virus together
with its transcriptional enzyme complex in both
quiescent and transcribing states.
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Corrigendum: A basal
ichthyosauriform with a short snout from the Lower
Triassic of China
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Communications
Arising |
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Cleavage of GSDMD by
inflammatory caspases determines pyroptotic cell
death
CRISPR-Cas9
genome-editing screens identify gasdermin D as a
substrate for inflammatory caspases, and its N-terminal
cleavage fragment, as well as the equivalent regions in
other gasdermins, is shown to be capable of inducing
pyroptosis.
Jianjin
Shi, Yue Zhao, Kun Wang et al. |
Caspase-11 cleaves
gasdermin D for non-canonical inflammasome
signalling
Gasdermin D is
identified as the required substrate for pyroptosis,
mediating caspase-11 function in the non-canonical
inflammasome pathway; the cleaved N-terminal domain is
shown to trigger pyroptosis.
Nobuhiko
Kayagaki, Irma B. Stowe, Bettina L. Lee et
al. |
Projections from
neocortex mediate top-down control of memory
retrieval
Here, a sparse
neuronal projection from a part of the prefrontal
cortex, the anterior cingulate, to the hippocampus is
identified that, when activated, can elicit memory
retrieval in mice.
Priyamvada
Rajasethupathy, Sethuraman Sankaran, James H. Marshel
et al. |
Selective
small-molecule inhibition of an RNA structural
element
A novel drug,
ribocil, is shown to mimic the binding of a natural
ligand to a bacterial riboflavin riboswitch (a
non-coding stretch of messenger RNA whose structure is
affected by a ligand—usually one related to the function
of the protein encoded by the messenger RNA) to cause
inhibition of bacterial growth; the ability to target an
RNA structural element with a synthetic small molecule
may expand our view of the target space susceptible to
therapeutic intervention.
John
A. Howe, Hao Wang, Thierry O. Fischmann et
al. | |
Telomerase activation
by genomic rearrangements in high-risk
neuroblastoma
Activation of
telomere maintenance mechanisms—caused by novel somatic
rearrangements of TERT, by MYCN
amplification, or ATRX mutations—is a hallmark of
high-risk neuroblastomas.
Martin
Peifer, Falk Hertwig, Frederik Roels et
al. |
Thalamic control of
sensory selection in divided attention
The
authors trained mice to attend to or suppress vision
based on behavioral context and show, through novel and
established techniques, that changes in visual gain rely
on tunable feedforward inhibition of visual thalamus via
innervating thalamic reticular neurons; these findings
introduce a subcortical model of attention in which
modality-specific thalamic reticular subnetworks mediate
top-down and context-dependent control of sensory
selection.
Ralf
D. Wimmer, L. Ian Schmitt, Thomas J. Davidson et
al. |
The earliest
unequivocally modern humans in southern China
A
collection of 47 unequivocally modern human teeth from a
cave in southern China shows that modern humans were in
the region at least 80,000 years ago, and possibly as
long as 120,000 years ago, which is twice as long as the
earliest known modern humans in Europe; the population
exhibited more derived features than contemporaneous
hominins in northern and central China, adding to the
complexity of the human story.
Wu
Liu, María Martinón-Torres, Yan-jun Cai et
al. |
Crystal structure of
the 500-kDa yeast acetyl-CoA carboxylase holoenzyme
dimer
Acetyl-CoA
carboxylases (ACCs) are large, multi-domain enzymes with
crucial functions in fatty acid metabolism and are
potential drug targets; here the X-ray crystal structure
of the full-length, 500-kDa holoenzyme dimer of the ACC
from Saccharomyces cerevisiae is solved and
reveals an organization quite different from that of
other biotin-dependent carboxylases.
Jia
Wei, Liang Tong |
Organometallic
palladium reagents for cysteine
bioconjugation
Palladium(ii)
complexes can be used in efficient and highly selective
cysteine conjugation reactions that are rapid and
robust, and the resulting aryl bioconjugates are stable
towards acids, bases, oxidants and external thiol
nucleophiles.
Ekaterina
V. Vinogradova, Chi Zhang, Alexander M. Spokoyny et
al. |
Decadal slowdown of a
land-terminating sector of the Greenland Ice Sheet
despite warming
Whether or not
an increase in meltwater will make ice sheets move more
quickly has been contentious, because water lubricates
the ice–rock interface and speeds up the ice, but also
stimulates the development of efficient drainage; now, a
long-term and large-area study of a land-terminating
margin of the Greenland Ice Sheet finds that more
meltwater does not equal higher
velocity.
Andrew
J. Tedstone, Peter W. Nienow, Noel Gourmelen et
al. |
Bacteriocin production
augments niche competition by enterococci in the
mammalian gastrointestinal tract
The authors
develop a mouse model of Enterococcus faecalis
colonization to show that enterococci harbouring the
bacteriocin-expressing plasmid pPD1 replace indigenous
enterococci and have the ability to transfer the plasmid
to other enterococci, which enhances the stability of
the bacteriocin-expressing bacteria in the gut; this
result suggests a therapeutic approach that leverages
niche-specificity to eliminate antibiotic-resistant
bacteria from infected individuals.
Sushma
Kommineni, Daniel J. Bretl, Vy Lam et
al. |
Abundant molecular
oxygen in the coma of comet
67P/Churyumov–Gerasimenko
In situ
measurement of O2 in the coma of comet
67P/Churyumov–Gerasimenko shows local abundances ranging
from one per cent to ten per cent relative to
H2O; the spatial and temporal uniformity of
the O2/H2O ratio suggests that
primordial O2 was incorporated into the
nucleus during the comet’s formation.
A.
Bieler, K. Altwegg, H. Balsiger et al.
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Yap-dependent
reprogramming of Lgr5+ stem cells drives
intestinal regeneration and cancer
This study finds
that the Hippo pathway is essential for gut epithelial
regeneration and tumour initiation; the Hippo component
Yap holds off differentiation of intestinal stem cells
to Paneth cells to promote a survival and self-renewal
regenerative program through activation of the Egfr
pathway.
Alex
Gregorieff, Yu Liu, Mohammad R. Inanlou et
al. |
CMT2D neuropathy is
linked to the neomorphic binding activity of glycyl-tRNA
synthetase
Charcot–Marie–Tooth
diseases are hereditary peripheral neuropathies for
which there are currently no effective therapies; here
the type 2D subtype of these diseases is shown to be
caused by mutations impeding a signalling pathway
necessary for motor neuron survival.
Weiwei
He, Ge Bai, Huihao Zhou et al. |
Loophole-free Bell
inequality violation using electron spins separated by
1.3 kilometres
A Bell
experiment that is ‘loophole’ free—leaving no room for
explanations based on experimental imperfections—reveals
a statistically significant conflict with local
realism
B.
Hensen, H. Bernien, A. E. Dréau et al.
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