| | Cell biology: Membrane kiss mediates hormone secretion
Communication between cells relies on hormone release from secretory granules, but how these vesicles fuse with cell membranes is unclear. An imaging study provides in vivo evidence for a stable intermediate fusion step. | Evolution: Gene regulation in transition
An in-depth analysis of a close relative of animals, Capsaspora owczarzaki, provides clues to the changes in gene regulation that occurred during the transition to multicellularity. | Structural biology: When sperm meets egg
Sperm–egg binding is mediated by two cell-surface proteins. Structural analysis of these proteins separately and in complex provides insight into the recognition process and the subsequent sperm–egg fusion. | Microbiology: The dark side of antibiotics
Interactions in the gut between host cells and bacteria can determine a state of health or disease. A study investigates how antibiotic treatment can affect host cells in a way that drives growth of pathogenic bacteria. | Biogeochemistry: Synergy of a warm spring and dry summer
An analysis suggests that high carbon uptake by US land ecosystems during the warm spring of 2012 offset the carbon loss that resulted from severe drought over the summer — and hints that the warm spring could have worsened the drought. | Crystal structure of the epithelial calcium channel TRPV6
The X-ray crystal structure of rat transient receptor potential channel TRPV6 at 3.25 Å resolution is reported, providing new insights into its assembly and calcium-selective permeation. | Defining the consequences of genetic variation on a proteome-wide scale
The effect of natural genetic diversity on the proteome is characterized using an outbred mouse model with extensive variation; both transcripts and proteins from mouse livers are quantified to identify a large set of protein quantitative trait loci (pQTL), and mediation analysis identifies causal protein intermediates of distant pQTL. | The landscape of accessible chromatin in mammalian preimplantation embryos
n improved ATAC-seq approach is used to describe a genome-wide view of accessible chromatin and cis-regulatory elements in mouse preimplantation embryos, allowing construction of a regulatory network of early development that helps to identify key modulators of lineage specification. | Negative capacitance in multidomain ferroelectric superlattices
Negative capacitance is observed in a model system of multidomain ferroelectric–dielectric superlattices; the multidomain state can increase the temperature range over which negative capacitance can be observed. | Abiological catalysis by artificial haem proteins containing noble metals in place of iron
Replacing the iron atom in Fe-porphyrin IX proteins with a noble-metal atom enables the creation of enzymes that catalyse reactions not catalysed by native Fe-enzymes or other metalloenzymes; this approach could be used to generate other artificial enzymes that could catalyse a wide range of abiological transformations. | Single-molecule strong coupling at room temperature in plasmonic nanocavities
Placing a light emitter in an ultra-small optical cavity results in coupling between matter and light, generating new forms of emission that can be exploited in practical or fundamental applications; here, a system is described in which strong light–matter coupling occurs at room temperature and in ambient conditions by aligning single dye molecules in the optical cavities between gold nanoparticles and surfaces. | Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor
The cancer drug rocaglamide A cements the RNA helicase eIF4A on polypurine sequences and thereby prevents scanning of the 43S subunit along the messenger RNA, highlighting how a drug can act by stabilizing sequence-selective RNA–protein interactions. | Subduction controls the distribution and fragmentation of Earth’s tectonic plates
Computer models of mantle convection with plate-like behaviour are used to demonstrate that the size–frequency distribution of tectonic plates on Earth is controlled by subduction geometry—the spacing between subducting slabs controls the layout of large plates, and the stresses caused by the bending of trenches break plates into smaller fragments. | Proteome-wide covalent ligand discovery in native biological systems
Small molecules are powerful tools for investigating protein function, and can serve as leads for new therapeutics, but most human proteins lack known small-molecule ligands; here, a quantitative analysis of cysteine-reactive small-molecule fragments screened against thousands of proteins is reported. | Design of a hyperstable 60-subunit protein icosahedron
The computational design of an extremely stable icosahedral self-assembling protein nanocage is presented; the icosahedron should be useful for applications ranging from calibrating fluorescence microscopy to drug delivery. | AMPK–SKP2–CARM1 signalling cascade in transcriptional regulation of autophagy
An investigation into the nuclear events involved in autophagy regulation identifies the histone arginine methyltransferase CARM1 as a transcriptional co-activator of transcription factor TFEB; CARM1 levels are decreased by the SKP2-containing E3 ubiquitin ligase and increased during autophagy induction after nutrient starvation. | The bacteriophage ϕ29 tail possesses a pore-forming loop for cell membrane penetration
Structural and functional studies of the tail knob protein of bacteriophage ϕ29 shed light on how the phage breaches the membrane barrier and ejects its DNA genome into the host cell. | Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex
This study describes the structures of the IZUMO1 protein, found on sperm, and the JUNO protein, found on eggs, and sheds light on their roles in sperm–egg fusion during fertilization. | Structure of IZUMO1–JUNO reveals sperm–oocyte recognition during mammalian fertilization
The structure of the IZUMO1–JUNO complex, crucial for sperm–oocyte interaction during fertilization, is reported, providing a first step towards understanding the mechanics of the interaction. | Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion
Antibiotic usage in humans can increase the risk of Salmonella infection by an unknown mechanism; this paper reveals that the antibiotic streptomycin increases the activity of the host-encoded enzyme inducible nitric oxide synthase, this then drives Salmonella expansion by the generation of galactarate — a metabolite normally absent from the gut. | Hemi-fused structure mediates and controls fusion and fission in live cells
Super-resolution imaging provides direct evidence in live cells that membrane fusion and fission are mediated through an intermediate hemi-fused structure, where fusion and calcium/dynamin-dependent fission mechanisms compete to determine the transition of the intermediate to fusion or fission. | Bright spots among the world’s coral reefs
Data from over 2,500 reefs worldwide is used to identify 15 bright spots—sites where reef biomass is significantly higher than expected—and surveys of local experts in these areas suggest that strong sociocultural institutions and high levels of local engagement are among the factors supporting higher fish biomass. | | | |
Nature Collection: Computational Biology Advances in technology across all areas of science have ushered in an era of big data, providing researchers with unprecedented opportunities to understand how biological systems function and interact. Access this collection free online for six months Produced with support from:
IBM Research & IBM Watson Health | | | | | | | | Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells
Leukaemic stem cells (LSCs) are responsible for BCR–ABL-driven chronic myeloid leukaemia relapse; here, p53 and MYC signalling networks are shown to regulate LSCs concurrently, and targeting both these pathways has a synergistic effect in managing the disease.
Sheela A. Abraham, Lisa E. M. Hopcroft, Emma Carrick et al. | TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action
Cryo-electron microscopy has undergone a resolution revolution—here, this method has been combined with lipid nanodisc technology to solve structures of TRPV1, the receptor for capsaicin, in a membrane bilayer, revealing mechanisms of lipid and ligand regulation.
Yuan Gao, Erhu Cao, David Julius et al. | Stem cell function and stress response are controlled by protein synthesis
The protein translation rate is low in tissue stem cells and tumour-initiating cells, and genetically preventing cytosine-5 methylation on transfer RNA in skin tumours is shown to favour the maintenance of a state of translational inhibition in mice, with tumour-initiating cells in this state becoming more sensitive to cytotoxic stress.
Sandra Blanco, Roberto Bandiera, Martyna Popis et al. | | Mean first-passage times of non-Markovian random walkers in confinement
An analytical method of determining the mean first-passage time (the time taken by a random walker in confinement to reach a target point) is presented for a Gaussian non-Markovian random walker, thus revealing the importance of memory effects in first-passage statistics.
T. Guérin, N. Levernier, O. Bénichou et al. | Structural basis for amino acid export by DMT superfamily transporter YddG
The X-ray structure of the drug/metabolite transporter (DMT) protein YddG from Starkeya novella reveals a new membrane transport topology, with ten transmembrane segments in an outward-facing state and two pseudo-symmetric inverted structural repeats.
Hirotoshi Tsuchiya, Shintaro Doki, Mizuki Takemoto et al. | Seafloor geodetic constraints on interplate coupling of the Nankai Trough megathrust zone
Seafloor geodetic data from the Nankai Trough, off southwestern Japan, show that most offshore sites in this earthquake-prone region have high slip-deficit rates, revealing previously unknown locations that could be important for the mitigation of future earthquake- and tsunami-associated disasters.
Yusuke Yokota, Tadashi Ishikawa, Shun-ichi Watanabe et al. | The bacterial DnaA-trio replication origin element specifies single-stranded DNA initiator binding
The bacterial chromosome replication origin contains an indispensable element composed of a repeating trinucleotide motif, termed the DnaA-trio, that stabilizes DnaA binding on single-stranded DNA.
Tomas T. Richardson, Omar Harran, Heath Murray | Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy
The development of a nanoparticle RNA vaccine is reported that preferentially targets dendritic cells after systemic administration, and is shown to provide durable interferon-α-dependent antigen-specific immunity in mouse tumour models; initial results in advanced melanoma patients indicate potential efficacy in humans.
Lena M. Kranz, Mustafa Diken, Heinrich Haas et al. | Fission and reconfiguration of bilobate comets as revealed by 67P/Churyumov–Gerasimenko
A modelling study of the bilobate nucleus of comet 67P/Churyumov–Gerasimenko reveals that it has spun much faster in the past, but that its chaotically changing spin rate has so far prevented it from splitting; eventually the two lobes will separate, but they will be unable to escape each other and will ultimately merge again—a situation that seems to be common among cometary nuclei.
Masatoshi Hirabayashi, Daniel J. Scheeres, Steven R. Chesley et al. | Intrinsic ferroelectric switching from first principles
Molecular dynamics simulations of 90° domain walls in PbTiO3 are used to construct a nucleation-and-growth-based analytical model that quantifies the dynamics of many types of domain walls in various ferroelectrics, suggesting intrinsic domain-wall motion as a universal mechanism for ferroelectric switching.
Shi Liu, Ilya Grinberg, Andrew M. Rappe | Neural correlates of single-vessel haemodynamic responses in vivo
Functional imaging techniques use changes in blood flow to infer neural activity, but how strongly the two are correlated is a subject of debate; here, vascular and neural responses to a range of visual stimuli are imaged in cat and rat primary visual cortex, revealing that vascular signals are partially decoupled from local neural signals.
Philip O’Herron, Pratik Y. Chhatbar, Manuel Levy et al. | Co-repressor CBFA2T2 regulates pluripotency and germline development
A co-repressor protein, CBFA2T2, oligomerizes to stabilize its binding partner PRDM14 and the pluripotency factor OCT4 on chromatin, thus facilitating the transcriptional landscape underpinning the germline and pluripotent fate.
Shengjiang Tu, Varun Narendra, Masashi Yamaji et al. | Aberrant PD-L1 expression through 3′-UTR disruption in multiple cancers
Structural variations disrupting the 3′ region of PD-L1 are shown to aid immune evasion in a number of human cancers, including adult T-cell leukaemia/lymphoma, and in a mouse tumour model, CRISPR-Cas9-mediated deletion of the 3'-UTR of Pd-l1 is also shown to result in immune escape, suggesting that PD-L1 3′-UTR disruption could provide a diagnostic marker to identify patients who will benefit from anti-PD-1/PD-L1 therapy.
Keisuke Kataoka, Yuichi Shiraishi, Yohei Takeda et al. | Concerted nucleophilic aromatic substitution with 19F− and 18F−
Nucleophilic aromatic substitution (SNAr) is the most commonly used method to generate arenes that contain 18F for use in PET imaging; here, an unusual concerted SNAr reaction is presented that is not limited to electron-poor arenes.
Constanze N. Neumann, Jacob M. Hooker, Tobias Ritter | Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma
The stem cell determinant Musashi (Msi) is a key mediator of pancreatic cancer progression and therapy resistance.
Raymond G. Fox, Nikki K. Lytle, Dawn V. Jaquish et al. | Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease
Preclinical evaluation and optimization of mitochondrial replacement therapy reveals that a modified form of pronuclear transfer is likely to give rise to normal pregnancies with a reduced risk of mitochondrial DNA disease, but may need further modification to eradicate the disease in all cases.
Louise A. Hyslop, Paul Blakeley, Lyndsey Craven et al. | Self-assembly of microcapsules via colloidal bond hybridization and anisotropy
The self-assembly of colloidal particles into hollow micrometre-scale capsules is achieved through the combination of anisotropic particle morphology, deformable surface ligands that re-distribute on binding and the mutual attraction between particles, suggesting a design strategy for colloidal self-assembly
Chris H. J. Evers, Jurriaan A. Luiken, Peter G. Bolhuis et al. | Dissecting direct reprogramming from fibroblast to neuron using single-cell RNA-seq
The transcriptome changes driving the conversion of fibroblasts to neurons at the single-cell level are reported, revealing that early neuronal reprogramming steps are homogenous, driven by the proneural pioneer factor Ascl1; the expression of myogenic genes then has a dampening effect on efficiency, which needs to be counteracted by the neuronal factors Myt1l and Brn2 for more efficient reprogramming.
Barbara Treutlein, Qian Yi Lee, J. Gray Camp et al. | | | | |
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