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Chromosomal
instability drives metastasis through a cytosolic DNA
response
In chromosomally
unstable tumour cells, rupture of micronuclei exposes
genomic DNA and activates the cGAS–STING cytosolic
DNA-sensing pathway, thereby promoting
metastasis. |
Midbrain
circuits that set locomotor speed and gait
selection
Speed and gait
selection in mice are controlled by glutamatergic
excitatory neurons in the cuneiform nucleus and the
pedunculopontine nucleus, which act in conjunction to
select context-dependent locomotor
behaviours. |
α-Klotho is a
non-enzymatic molecular scaffold for FGF23 hormone
signalling
The crystal
structure of shed ectodomain of α-klotho bound to the
FGFR1c ligand-binding domain and FGF23 unveils the
mechanism by which klotho co-receptors promote hormonal
FGF signalling. |
Structures of
β-klotho reveal a ‘zip code’-like mechanism for
endocrine FGF signalling
Crystal
structures of free and ligand-bound β-klotho reveal that
it acts as a primary receptor for FGF21, and demonstrate
how a sugar-cutting enzyme has evolved to become a
receptor for hormones that regulate metabolic
processes. |
Centimetre-scale
electron diffusion in photoactive organic
heterostructures
For a suitably
designed organic multilayer structure, optically or
electrically generated electrons confined to a thin
fullerene channel can diffuse over surprisingly long
distances of several centimetres. |
Observation
of a phononic quadrupole topological
insulator
A
two-dimensional phononic quadrupole topological
insulator is demonstrated experimentally using
mechanical metamaterials, which has both the
one-dimensional edge states and the zero-dimensional
corner states predicted by theory. |
Clonal
evolution mechanisms in NT5C2 mutant-relapsed
acute lymphoblastic leukaemia
Mutations in the
nucleotidase-encoding gene NT5C2 drive
chemotherapy resistance in relapsed acute lymphoid
leukaemia but the mutations also lead to a
loss-of-fitness phenotype and to collateral drug
sensitivity, which could be exploited for
therapy. |
A Myc
enhancer cluster regulates normal and leukaemic
haematopoietic stem cell hierarchies
A blood enhancer
cluster forms a highly combinatorial system that allows
precise control of Myc expression across normal
and leukaemic haematopoietic stem cell
hierarchies. |
Regulation of
embryonic haematopoietic multipotency by
EZH1
The production
of haematopoietic stem cells is repressed during early
mammalian embryogenesis by an epigenetic mechanism that
involves the action of the Polycomb protein
EZH1. |
Structure
and mutagenesis reveal essential capsid protein
interactions for KSHV replication
Cryo-electron
microscopy reveals the structure of the Kaposi’s
sarcoma-associated herpesvirus capsid, and experiments
with polypeptides that mimic the smallest capsid protein
demonstrate the potential for structure-derived insights
to help to develop antiviral agents. |
Atomic
structure of the eukaryotic intramembrane RAS
methyltransferase ICMT
The X-ray
structure of the integral membrane protein
isoprenylcysteine carboxyl methyltransferase suggests
mechanisms by which it recognizes both water-soluble and
membrane-bound reactants to catalyse the methylation of
RAS and other CAAX proteins at the membrane-cytosol
interface. |
Monitoring T
cell–dendritic cell interactions in vivo by
intercellular enzymatic labelling
Interactions
between receptors and ligands on immune cells are
visualized in vivo and in vitro using an
enzyme-tagged ligand that, when cells interact, leaves
behind a detectable label on the receptor-expressing
cell. |
| Erratum:
Moving beyond microbiome-wide associations to causal
microbe identification |
| Corrigendum:
mTORC1-dependent AMD1 regulation sustains polyamine
metabolism in prostate
cancer | |
Dietary
trehalose enhances virulence of epidemic Clostridium
difficile
Two
hypervirulent ribotypes of the enteric pathogen
Clostridium difficile, RT027 and RT078, have
independently acquired unique mechanisms to metabolize
low concentrations of the disaccharide trehalose,
suggesting a correlation between the emergence of these
ribotypes and the widespread adoption of trehalose in
the human diet.
J.
Collins, C. Robinson, H. Danhof et
al. |
Molecular
mechanism of promoter opening by RNA polymerase
III
Cryo-EM
structures of Pol III preinitiation complexes are
presented, comprising Pol III and the transcription
factor TFIIIB bound to a natural promoter in different
functional states.
Matthias
K. Vorländer, Heena Khatter, Rene Wetzel et
al. |
Structural
basis of RNA polymerase III transcription
initiation
Detailed
structures of yeast RNA polymerase III and its
initiation complex shed light on how the transcription
of essential non-coding RNAs begins and allow
comparisons with other RNA polymerases.
Guillermo
Abascal-Palacios, Ewan Phillip Ramsay, Fabienne Beuron
et
al. | |
Black-hole-regulated
star formation in massive galaxies
The star
formation histories of galaxies, as encapsulated in
their integrated optical spectra, depend on the mass of
the black holes present at their
centres.
Ignacio
Martín-Navarro, Jean P. Brodie, Aaron J. Romanowsky
et al. |
Large
granulation cells on the surface of the giant star
π1 Gruis
Interferometric
images of the surface of the giant star π1
Gruis reveal few but large convective cells, consistent
with existing models of stellar surface
convection.
C.
Paladini, F. Baron, A. Jorissen et
al. |
A record of
deep-ocean dissolved O2 from the oxidation
state of iron in submarine basalts
Deep-ocean
O2 concentrations over the past 3.5 billion
years are estimated using the oxidation state of iron in
submarine basalts and indicate that deep-ocean
oxygenation occurred in the Phanerozoic
eon.
Daniel
A. Stolper, C. Brenhin Keller |
Paternal
chromosome loss and metabolic crisis contribute to
hybrid inviability in Xenopus
In hybrid
inviability between Xenopus laevis and Xenopus
tropicalis, genomic regions on two X. laevis
chromosomes are incompatible with the X.
tropicalis cytoplasm and are mis-segregated during
mitosis, leading to unbalanced gene expression at the
maternal to zygotic transition, followed by
cell-autonomous catastrophic embryo
death.
Romain
Gibeaux, Rachael Acker, Maiko Kitaoka et
al. |
Pharmacological
activation of REV-ERBs is lethal in cancer and
oncogene-induced senescence
REV-ERBs,
nuclear hormone receptors that regulate transcription as
part of the circadian clock cell machinery, inhibit
autophagy and lipogenesis in premalignant and malignant
cells and impair tumour growth in
vivo.
Gabriele
Sulli, Amy Rommel, Xiaojie Wang et
al. |
AMD1
mRNA employs ribosome stalling as a mechanism for
molecular memory formation
A regulatory
mechanism that limits the number of complete protein
molecules that can be synthesized from a single mRNA
molecule of the human AMD1 gene encoding
adenosylmethionine decarboxylase 1.
Martina
M. Yordanova, Gary Loughran, Alexander V. Zhdanov et
al. |
Systems of
mechanized and reactive droplets powered by
multi-responsive surfactants
Droplets covered
with surfactants that respond to multiple stimuli can
assemble into hierarchical assemblies or non-spherical,
patchy structures, mimic systems of mechanical gears,
and even harbour sequences of chemical
reactions.
Zhijie
Yang, Jingjing Wei, Yaroslav I. Sobolev et
al. |
Emergent
constraint on equilibrium climate sensitivity from
global temperature variability
Equilibrium
climate sensitivity—which remains the largest
uncertainty in climate projections—is constrained to a
‘likely’ range of 2.2–3.4 K by taking into account the
variability of global temperature about long-term
historical warming.
Peter
M. Cox, Chris Huntingford, Mark S.
Williamson |
Warfare and
wildlife declines in Africa’s protected
areas
Assessment of
the impact of armed conflict on large herbivores in
Africa between 1946 and 2010 reveals that high conflict
frequency is an important predictor of wildlife
population declines.
Joshua
H. Daskin, Robert M. Pringle |
A global map
of travel time to cities to assess inequalities in
accessibility in 2015
Travel time to
cities in 2015 is quantified in a high-resolution global
map that will be useful for socio-economic policy design
and conservation research.
D.
J. Weiss, A. Nelson, H. S. Gibson et
al. |
An
extracellular network of Arabidopsis leucine-rich
repeat receptor kinases
A
high-throughput assay is used to analyse 40,000
potential extracellular domain interactions of a large
family of plant cell surface receptors (LRR-RKs) and
provide a cell surface interaction network for these
receptors.
Elwira
Smakowska-Luzan, G. Adam Mott, Katarzyna Parys et
al. |
High
response rate to PD-1 blockade in desmoplastic
melanomas
Immune
checkpoint blockade with anti-PD-1 or anti-PD-L1 agents
produces a high response rate in patients with
desmoplastic melanoma.
Zeynep
Eroglu, Jesse M. Zaretsky, Siwen Hu-Lieskovan et
al. |
Architecture
of a channel-forming O-antigen polysaccharide ABC
transporter
The crystal
structure of a channel-forming O-antigen polysaccharide
ABC transporter suggests a novel biopolymer
translocation mechanism.
Yunchen
Bi, Evan Mann, Chris Whitfield et
al. | |
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