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Cancer: An essential passenger with p53
Deletion of the TP53 gene, an event seen in colorectal cancers, often occurs with co-deletion of a gene that encodes an enzyme subunit governing gene transcription. This creates a vulnerability ripe for therapeutic development.
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Ecology: Tasteless pesticides affect bees in the field
Two studies provide evidence that bees cannot taste or avoid neonicotinoid pesticides, and that exposure to treated crops affects reproduction in solitary bees as well as bumblebee colony growth and reproduction.
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A multilevel multimodal circuit enhances action selection in Drosophila
Combining neural manipulation in freely behaving animals, physiological studies and electron microscopy reconstruction in the Drosophila larva identifies a complex multilsensory circuit involved in the selection of larval escape modes that exhibits a multilevel multimodal convergence architecture.
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Structure of the human 80S ribosome
The structure of the human ribosome at high resolution has been solved; by combining single-particle cryo-EM and atomic model building, local resolution of 2.9 Å was achieved within the most stable areas of the structure.
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Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans
Mitophagy, a selective type of autophagy targeting mitochondria for degradation, interfaces with mitochondrial biogenesis to regulate mitochondrial content and longevity in Caenorhabditis elegans.
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Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells
The human endogenous retrovirus HERVK is normally silenced, but here the surprising discovery is made that in early human embryo development it is expressed, producing retroviral-like particles.
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Alternative 3′ UTRs act as scaffolds to regulate membrane protein localization
Many human genes undergo alternative cleavage and polyadenylation to generate messenger RNA transcripts with different lengths at the 3' untranslated regions (3' UTRs) but that encode the same protein; now it is shown that these alternative 3' UTRs regulate protein localization.
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Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo
Two drugs, miconazole and clobetasol, have functions that modulate differentiation of oligodendrocyte progenitor cells directly, enhance remyelination, and significantly reduce disease severity in mouse models of multiple sclerosis.
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Topological valley transport at bilayer graphene domain walls
The bandgap of bilayer graphene can be tuned with an electric field and topological valley polarized modes have been predicted to exist at its domain boundaries; here, near-field infrared imaging and low-temperature transport measurements reveal such modes in gapped bilayer graphene.
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Bees prefer foods containing neonicotinoid pesticides
It has been suggested that the negative effects on bees of neonicotinoid pesticides could be averted in field conditions if they chose not to forage on treated nectar; here field-level neonicotinoid doses are used in laboratory experiments to show that honeybees and bumblebees do not avoid neonicotinoid-treated food and instead actually prefer it.
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TP53 loss creates therapeutic vulnerability in colorectal cancer
Genomic deletion of the tumour suppressor TP53 frequently includes other neighbouring genes, such as the POLR2A housekeeping gene that encodes a crucial RNA polymerase II subunit; suppression of POLR2A with α-amanitin or by RNA interference selectively inhibits the tumorigenic potential of cancer cells, and in mouse models of cancer, tumours can be selectively targeted with α-amanitin coupled to antibodies, suggesting new therapeutic approaches for human cancers.
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Seed coating with a neonicotinoid insecticide negatively affects wild bees
Neonicotinoid seed coating is associated with reduced density of wild bees, as well as reduced nesting of solitary bees and reduced colony growth and reproduction of bumblebees, but appears not to affect honeybees.
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Mutant MHC class II epitopes drive therapeutic immune responses to cancer
The authors show that a large fraction of tumour mutations is immunogenic and predominantly recognized by CD4+ T cells; they use these data to design synthetic messenger-RNA-based vaccines specific against tumour mutations, and show that these can reject tumours in mice.
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Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates
Ebola-virus-targeting short interfering RNAs (siRNAs) encapsulated in lipid nanoparticles are adapted to the current outbreak strain of the virus, and the siRNA cocktail is shown to protect nonhuman primates fully when administered 3 days after challenge with the current West African Ebola virus isolate; upon viral sequence data availability, the drug can be adapted to the new virus and produced in as little as 8 weeks.
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CRISPR adaptation biases explain preference for acquisition of foreign DNA
In the bacterial immunity system CRISPR, spacer acquisition is facilitated near replication-termination regions.
Asaf Levy, Moran G. Goren, Ido Yosef et al. |
Structure of the TRPA1 ion channel suggests regulatory mechanisms
The high-resolution electron cryo-microscopy structure of the full-length human TRPA1 ion channel is presented; the structure reveals a unique ankyrin repeat domain arrangement, a tetrameric coiled-coil in the centre of the channel that acts as a binding site for inositol hexakisphosphate, an outer poor domain with two pore helices, and a new drug binding site, findings that collectively provide mechanistic insight into TRPA1 regulation.
Candice E. Paulsen, Jean-Paul Armache, Yuan Gao et al. |
Oxytocin enables maternal behaviour by balancing cortical inhibition
A study of pup retrieval behaviour in mice shows that oxytocin modulates cortical responses to pup calls specifically in the left auditory cortex; in virgin females, call-evoked responses were enhanced, thus increasing their salience, by pairing oxytocin delivery in the left auditory cortex with the calls, suggesting enhancement was a result of balancing the magnitude and timing of inhibition with excitation.
Bianca J. Marlin, Mariela Mitre, James A. D’amour et al. |
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Eocene primates of South America and the African origins of New World monkeys
The discovery of new primates from the ?Late Eocene epoch of Amazonian Peru extends the fossil record of primates in South America back approximately 10 million years.
Mariano Bond, Marcelo F. Tejedor, Kenneth E. Campbell Jr et al. |
Mitochondrial DNA stress primes the antiviral innate immune response
Mitochondrial DNA stress potentiates type I interferon responses via activation of the cGAS–STING–IRF3 pathway.
A. Phillip West, William Khoury-Hanold, Matthew Staron et al. |
Tungsten isotopic evidence for disproportional late accretion to the Earth and Moon
Examination of three lunar samples reveals that the Moon’s mantle has an excess of the tungsten isotope 182W of about 20 parts per million relative to the present-day Earth’s mantle; this suggests that the two bodies had identical compositions immediately following the formation of the Moon, and that the compositions then diverged as a result of disproportional late accretion of chondritic material to the Earth and Moon.
Mathieu Touboul, Igor S. Puchtel, Richard J. Walker |
Phylogenetic structure and host abundance drive disease pressure in communities
Rare species may have an advantage in a community by suffering less from disease; here it is shown that, because pathogens are shared among species, it is not just the abundance of a particular species but the structure of the whole community that affects exposure to disease.
Ingrid M. Parker, Megan Saunders, Megan Bontrager et al. |
ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes
The essential autophagy mediator ATG14 promotes vesicle fusion by forming homo-oligomers, which bind to a component of the SNARE membrane fusion complex and stabilize this complex on autophagosomes.
Jiajie Diao, Rong Liu, Yueguang Rong et al. |
Self-similar fragmentation regulated by magnetic fields in a region forming massive stars
Polarimetric observations of magnetic-field orientations in a filamentary molecular cloud forming massive stars shows that the magnetic field strongly affects fragmentation in the region.
Hua-bai Li, Ka Ho Yuen, Frank Otto et al. |
Super-enhancers delineate disease-associated regulatory nodes in T cells
A study of the super-enhancer landscape in three mouse T-helper lymphocyte subsets identifies nodes that have key roles in cell identity, with the locus encoding Bach2, a key negative regulator of effector differentiation, emerging as the most prominent T-cell super-enhancer.
Golnaz Vahedi, Yuka Kanno, Yasuko Furumoto et al. |
Agrochemical control of plant water use using engineered abscisic acid receptors
In response to water shortage, plants produce abscisic acid (ABA), which improves water consumption and stress tolerance; now, a strategy for controlling water use by activating engineered ABA receptors using an existing agrochemical, mandipropamid, is described.
Sang-Youl Park, Francis C. Peterson, Assaf Mosquna et al. |
In situ low-relief landscape formation as a result of river network disruption
The relict landscapes of southeast Tibet are being formed in situ as a result of river drainage reorganization that renders rivers unable to balance tectonic uplift, so these landscapes may not provide an unaltered record of past geomorphic conditions.
Rong Yang, Sean D. Willett, Liran Goren |
Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells
Here, DNA damage is shown to occur as a direct consequence of inducing haematopoietic stem cells to exit quiescence in response to conditions of stress; in mice with mutations modelling those seen in Fanconi anaemia, this leads to a complete collapse of the haematopoietic system.
Dagmar Walter, Amelie Lier, Anja Geiselhart et al. |
Structure of the E. coli ribosome–EF-Tu complex at <3 Å resolution by Cs-corrected cryo-EM
A single particle cryo-EM structure of the 70S ribosome in complex with the elongation factor Tu breaks the 3 Å resolution barrier of the technique and locally exceeds the resolution of previous crystallographic studies, revealing all modifications in rRNA and explaining their roles in ribosome function and antibiotic binding.
Niels Fischer, Piotr Neumann, Andrey L. Konevega et al. |
Phonon counting and intensity interferometry of a nanomechanical resonator
A silicon nanometre-scale mechanical resonator, patterned to couple optical and mechanical resonances, is found to emit photons when optically pumped; photon emission corresponds directly to phonon emission, enabling the phonons to be counted.
Justin D. Cohen, Seán M. Meenehan, Gregory S. MacCabe et al. |
Lunar tungsten isotopic evidence for the late veneer
Precise measurements of the tungsten isotopic composition of lunar rocks show that the Moon exhibits a well-resolved excess of 182W of about 27 parts per million over the present-day Earth’s mantle: this excess is consistent with the expected 182W difference resulting from a late veneer with a total mass and composition inferred from previously measured highly siderophile elements.
Thomas S. Kruijer, Thorsten Kleine, Mario Fischer-Gödde et al. |
Hydrogens detected by subatomic resolution protein crystallography in a [NiFe] hydrogenase
A sub-ångström-resolution X-ray crystal structure of [NiFe] hydrogenase, with direct detection of the products of the heterolytic splitting of dihydrogen into a hydride bridging the Ni and Fe and a proton attached to the sulphur of a cysteine ligand.
Hideaki Ogata, Koji Nishikawa, Wolfgang Lubitz |
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