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Myeloid disease:
Another action of a thalidomide derivative
Lenalidomide
effectively treats a blood disorder caused by the 5q
chromosomal deletion. A study shows that the drug binds
to its target, CRBN, to promote the breakdown of an
enzyme encoded by a gene in the 5q region. |
Protistology: How to
build a microbial eye
Dissection of
the subcellular eye of microorganisms called warnowiid
dinoflagellates reveals that this structure is composed
of elements of two cellular organelles — the plastid and
the mitochondrion. |
Developmental biology:
Nanotubes in the niche
In fruit flies,
protrusions can extend from stem cells in the testes to
cells in a regulatory hub, mediating intercellular
signalling and stem-cell maintenance. The implications
of this finding are presented here from two
angles. |
Lenalidomide induces
ubiquitination and degradation of CK1α in del(5q)
MDS
Lenalidomide, a
derivative of thalidomide, is an effective drug for
myelodysplastic syndrome; lenalidomide binds the
CRL4CRBN E3 ubiquitin ligase and promotes
degradation of casein kinase 1a, on which the malignant
cells rely for survival. |
T-cell exhaustion,
co-stimulation and clinical outcome in autoimmunity and
infection
CD8 T-cell
exhaustion, although a negative prognostic indicator
during persistent infections, is shown to be associated
with a good outcome in autoimmune and inflammatory
diseases. |
Molecular basis for
5-carboxycytosine recognition by RNA polymerase II
elongation complex
Structural and
biochemical studies of RNA polymerase II (Pol II)
assembled on DNA containing 5-carboxycytosine reveals
that Pol II can sense the oxidized methylation state of
DNA and transiently slows down during
transcription. |
Identification of
cis-suppression of human disease mutations by
comparative genomics
Patterns of
amino acid conservation have been used to guide the
interpretation of the disease-causing potential of
genetic variants in patients; now, an appreciable
fraction of pathogenic alleles are shown to be fixed in
the genomes of other species, suggesting that the
genomic context has an important role in allele
pathogenicity. |
A hemi-fission
intermediate links two mechanistically distinct stages
of membrane fission
The GTPase
dynamin provides the driving force for fission of
membrane-bound vesicular structures; here, it is shown
that dynamin-driven membrane fission proceeds in two
mechanistically distinct stages that are separated by a
metastable hemi-fission intermediate that requires GTP
hydrolysis for progression to full fission. |
Global-scale coherence
modulation of radiation-belt electron loss from
plasmaspheric hiss
Simultaneous
measurements of structured radiation-belt electron
losses (in the form of bremsstrahlung X-rays) and
plasmaspheric hiss (which causes the losses) reveal that
the loss dynamics is coherent with the hiss dynamics on
spatial scales comparable to the size of the
plasmasphere. |
Eye-like ocelloids are
built from different endosymbiotically acquired
components
Dinoflagellate
eye-like ocelloids are built from pre-existing
organelles of disparate origin, including a cornea-like
layer made of mitochondria and a retinal body made of
anastomosing plastids. |
Viral-genetic tracing
of the input–output organization of a central
noradrenaline circuit
To better
understand the relationship between input and output
connectivity for neurons of interest in specific brain
regions, a viral-genetic tracing approach is used to
identify input based on a combination of neurons’
projection and cell type, as illustrated in a study of
locus coeruleus noradrenaline neurons. |
Nanotubes mediate
niche–stem-cell signalling in the Drosophila
testis
Drosophila male
germline stem cells form previously unrecognized
structures, microtubule-based nanotubes, which extend
into the hub, a major niche component, to mediate the
niche–stem-cell signalling. |
Influence maximization
in complex networks through optimal
percolation
A rigorous
method to determine the most influential superspreaders
in complex networks is presented—involving the mapping
of the problem onto optimal percolation along with a
scalable algorithm for big-data social networks—showing,
unexpectedly, that many weak nodes can be powerful
influencers. |
Directional dominance
on stature and cognition in diverse human
populations
An analysis of
16 health-related quantitative traits in approximately
350,000 individuals reveals statistically significant
associations between genome-wide homozygosity and four
complex traits (height, lung function, cognitive ability
and educational attainment); in each case increased
homozygosity associates with a decreased trait value,
but no evidence was seen of an influence on blood
pressure, cholesterol, or ten other cardio-metabolic
traits. |
| Corrigendum: Greenland
supraglacial lake drainages triggered by hydrologically
induced basal
slip | |
The architecture of
the spliceosomal U4/U6.U5 tri-snRNP
This study
determines the structure of the spliceosomal tri-snRNP
complex (containing three small nuclear RNAs and more
than 30 proteins) by single-particle cryo-electron
microscopy; the resolution is sufficient to discern the
organization of RNA and protein components involved in
spliceosome activation, exon alignment and
catalysis.
Thi
Hoang Duong Nguyen, Wojciech P. Galej, Xiao-chen Bai
et al. |
The core spliceosome
as target and effector of non-canonical ATM
signalling
Transcription-blocking
DNA lesions result in chromatin displacement of core
spliceosomes containing U2 and U5 snRNPs; consequently,
R-loops containing the nascent transcript are formed,
which activate ATM in a feed-forward fashion to
influence spliceosome dynamics and alternative
splicing.
Maria
Tresini, Daniël O. Warmerdam, Petros Kolovos et
al. | |
Self-similar
energetics in large clusters of galaxies
Massive galaxy
clusters are filled with a hot, turbulent and magnetized
intra-cluster medium, whose energy is derived from
gravitational energy; the energy components of this
medium are now shown to be ordered according to a
permanent hierarchy, in which the ratio of thermal to
turbulent to magnetic energy densities remains virtually
unaltered over time.
Francesco
Miniati, Andrey Beresnyak |
Large heterogeneities
in comet 67P as revealed by active pits from sinkhole
collapse
The size and
spatial distribution of pits on comet
67P/Churyumov–Gerasimenko, which are active and probably
created by a sinkhole process, imply that large
heterogeneities exist in the physical, structural or
compositional properties of the first few hundred metres
below the current cometary surface.
Jean-Baptiste
Vincent, Dennis Bodewits, Sébastien Besse et
al. |
A colloidal quantum
dot spectrometer
An efficient,
cost effective microspectrometer that consists of a
two-dimensional absorptive filter array of 195 different
colloidal quantum dots is presented, and its performance
demonstrated by measuring shifts in spectral peak
positions as small as one nanometre.
Jie
Bao, Moungi G. Bawendi |
A model-tested North
Atlantic Oscillation reconstruction for the past
millennium
The North
Atlantic Oscillation (NAO) is an important source of
climate variability in the Northern Hemisphere; here, a
model-tested reconstruction of the NAO for the past
millennium reveals that positive NAO phases were
predominant during the thirteenth and fourteenth
centuries, but not during the whole medieval
period.
Pablo
Ortega, Flavio Lehner, Didier Swingedouw et
al. |
Hallucigenia’s
head and the pharyngeal armature of early
ecdysozoans
A re-analysis of
the 508-million-year-old stem-group onychophoran
Hallucigenia sparsa from the Burgess Shale shows
that its anterior gut has structures that indicate
evolutionary links with more disparate phyla such as
nematodes and kinorhynchs; Hallucigenia now
provides concrete evidence of structures that might have
existed in the last common ancestor of the Ecdysozoa,
previously a matter of conjecture.
Martin
R. Smith, Jean-Bernard Caron |
Sex reversal triggers
the rapid transition from genetic to
temperature-dependent sex
The first report
of reptile sex reversal in the wild and rapid transition
between genetic and environmental sex determination in
the Australian bearded dragon (Pogona
vitticeps)
Clare
E. Holleley, Denis O'Meally, Stephen D. Sarre et
al. |
Spatiotemporal control
of a novel synaptic organizer molecule
Neuronal
synapses need to be formed at the right time and the
right place during nervous system development; here,
three gene-regulatory factors (the UNC-30, LIN-14 and
UNC-55 DNA-binding proteins) are shown to operate in an
intersectional manner to control the expression of a
novel synaptic organizer molecule,
OIG-1.
Kelly
Howell, John G. White, Oliver Hobert |
Cell-intrinsic
adaptation of lipid composition to local crowding drives
social behaviour
Little is known
about how individual cells within a group of cells
exposed to the same external signals can produce a
specific individual response to their local
microenvironment; a quantitative analysis of cell
crowding reveals that single cells can autonomously
sense local crowding though their ability to spread and
activate focal adhesion kinase (FAK), which ultimately
results in changes in cellular lipid
composition.
Mathieu
Frechin, Thomas Stoeger, Stephan Daetwyler et
al. |
Mechanical induction
of the tumorigenic β-catenin pathway by tumour growth
pressure
Magnetically
induced mechanical strain mimicking the pressure exerted
by a growing tumour in the mouse colon is shown to
activate the tumorigenic β-catenin pathway in healthy
epithelia, suggesting an alternative pathway,
mechanotransductive in nature, in the propagation of
tumorigenesis and growth from tumour to healthy
tissue.
María
Elena Fernández-Sánchez, Sandrine Barbier, Joanne
Whitehead et al. |
MYC regulates the core
pre-mRNA splicing machinery as an essential step in
lymphomagenesis
The critical
effectors of MYC overexpression during lymphomagenesis
in transgenic mice are defined.
Cheryl
M. Koh, Marco Bezzi, Diana H. P. Low et
al. |
Cytosolic extensions
directly regulate a rhomboid protease by modulating
substrate gating
Calcium potently
stimulates proteolysis by endogenous rhomboid-4, an
intramembrane protease that contains a cytoplasmic
calcium-binding EF-hand domain.
Rosanna
P. Baker, Siniša Urban |
Structures of
actin-like ParM filaments show architecture of
plasmid-segregating spindles
Structures of
actin-like ParM filaments at near-atomic resolution and
their arrangements into doublets reveal how subunits and
filaments come together to segregate low-copy-number
plasmid R1 in Escherichia coli, producing the simplest
known mitotic machinery.
Tanmay
A. M. Bharat, Garib N. Murshudov, Carsten Sachse et
al. |
Structures of human
phosphofructokinase-1 and atomic basis of
cancer-associated mutations
The first
structures of the mammalian phosphofructokinase-1
tetramer are reported, for the human platelet isoform,
in complex with ATP–Mg2+ and
ADP.
Bradley
A. Webb, Farhad Forouhar, Fu-En Szu et
al. | | |
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