| | Immunology: In the right place at the right time
Regulatory T cells help to prevent autoimmune responses. A new imaging technique reveals that activation of these cells requires clustering with self-reactive effector T cells and sensing of the signalling protein interleukin-2. | Structural biology: A transcriptional specialist resolved
Three structures of the enzyme RNA polymerase III, which is responsible for the synthesis of abundant short RNAs, reveal the specializations that make it an adept terminator and reinitiator of transcription. | Cell biology: Architecture of a protein entry gate
The TOM complex guides precursor proteins from the cell's cytosolic fluid into organelles called mitochondria. Biochemical analyses reveal the architecture of this complex and show how precursor proteins pass through its narrow pores. | Managing nitrogen for sustainable development
Careful management of nitrogen fertilizer usage is required to ensure world food security while limiting environmental degradation; an analysis of historical nitrogen use efficiency reveals socio-economic factors and technological innovations that have influenced a range of past national trends and that suggest ways to improve global food production and environmental stewardship by 2050. | Soil biodiversity and human health
Soil biodiversity sustains human health and its loss can be mitigated by sustainable management. | The contentious nature of soil organic matter
Instead of containing stable and chemically unique ‘humic substances’, as has been widely accepted, soil organic matter is a mixture of progressively decomposing organic compounds; this has broad implications for soil science and its applications. | Molecular structures of unbound and transcribing RNA polymerase III
RNA polymerase III (Pol III), the largest eukaryote polymerase yet characterized, transcribes structured small non-coding RNAs; here cryo-electron microscopy structures of budding yeast Pol III allow building of an atomic-level model of the complete 17-subunit complex, both unbound and while elongating RNA. | Genome-wide patterns of selection in 230 ancient Eurasians
The first genome-wide scan for selection using ancient DNA, based on data from 230 West Eurasians dating between to 6500 and 300 BC and including new data from 163 individuals among which are 26 Neolithic Anatolians, provides a direct view of selection on loci associated with diet, pigmentation and immunity. | Immune homeostasis enforced by co-localized effector and regulatory T cells
Autoantigen-presenting dendritic cells are shown to interact with both effector and regulatory T cells, and effector-produced IL-2 activates the transcription factor STAT5 in regulatory T cells, which in turn upregulates suppressive molecules and prevents autoimmunity. | Death from drought in tropical forests is triggered by hydraulics not carbon starvation
It has been suggested that carbon starvation, owing to reduced availability of non-structural carbohydrates (NSCs), is an important contributor to tree mortality during drought in tropical rainforests; however, data from the world’s longest-running experimental drought study presented here show no evidence of carbon starvation, and instead the researchers conclude that impaired water hydraulic processes (involving the transport of water from soil to leaf) have a more important role in triggering tree death from long-term drought. | Genome-wide detection of DNase I hypersensitive sites in single cells and FFPE tissue samples
A DNase sequencing method termed scDNase-seq detects DNase I hypersensitive sites genome-wide in single cells and pools of cells dissected from cancer biopsies. | Relativistic baryonic jets from an ultraluminous supersoft X-ray source
Persistent low-velocity baryonic jets have been detected from a supersoft X-ray source; the low velocity suggests that these jets have not been launched from a white dwarf, and the persistence speaks against the origin being a canonical black hole or neutron star, indicating that a different type of source must be implicated. | FGF signalling regulates bone growth through autophagy
During postnatal development in mice, the growth factor FGF18 induces autophagy in the chondrocyte cells of the growth plate to regulate the secretion of type II collagen, a process required for bone growth. | A mechanism for expansion of regulatory T-cell repertoire and its role in self-tolerance
Regulatory T cells need to express a diverse T-cell-receptor repertoire to control pathogenic self-reactive T cells; here it is shown that repertoire diversification depends on the intronic Foxp3 enhancer CNS3 acting at the regulatory T-cell-precursor stage to induce T-cell-receptor responsiveness to low-strength signals. | Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides
Genetic correction of MeCP2 levels largely reversed the behavioural, molecular and physiological deficits associated with MECP2 duplication syndrome in a transgenic mouse model; similarly, reduction of MeCP2 levels using an antisense oligonucleotide strategy resulted in phenotypic rescue in adult transgenic mice, and dose-dependently corrected MeCP2 levels in cells from patients with MECP2 duplication. | | Erratum: Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder | | Corrigendum: NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells | | Corrigendum: Human body epigenome maps reveal noncanonical DNA methylation variation | | Corrigendum: Acute stress facilitates long-lasting changes in cholinergic gene expression | | | | Primers in your inbox
Nature Reviews Disease Primers launched in April 2015 and publishes Primers — introductory review articles that provide overviews of diseases and disorders. Primer articles describe all aspects of a condition: epidemiology; disease mechanisms; diagnosis, screening and prevention; management; and quality of life. Stay updated on the latest Primers published. | | | | | | | | | | | | | Hemichordate genomes and deuterostome origins OPEN
Sequencing the genomes of two enteropneusts reveals complex genomic organization and developmental innovation in the ancestor of deuterostomes, a group of animals including echinoderms (starfish and their relatives) and chordates (which includes humans).
Oleg Simakov, Takeshi Kawashima, Ferdinand Marlétaz et al. | A perisinusoidal niche for extramedullary haematopoiesis in the spleen
Haematopoietic stem cells normally reside in a bone marrow niche but they are recruited to the spleen after physiological stresses; here, endothelial cells and stromal cells around sinusoidal blood vessels of the spleen are shown to secrete key niche factors to support this process.
Christopher N. Inra, Bo O. Zhou, Melih Acar et al. | Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance
An epithelial-to-mesenchymal transition (EMT) lineage-tracing system in a mouse model of breast-to-lung metastasis reveals that although some cells undergo EMT in a primary epithelial tumour, the lung metastases mainly arise from cells that have not undergone EMT; in addition, cells that have undergone EMT appear more resistant to chemotherapy.
Kari R. Fischer, Anna Durrans, Sharrell Lee et al. | Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65
Yeast-based screening identifies the benzodiazepine drug lorazepam as a non-selective positive allosteric modulator of the G-protein-coupled receptor (GPCR) GPR68; homology modelling and molecular docking of 3.1 million molecules found a new compound, ‘ogerin’, as a potent GPR68 modulator, which suppressed recall in fear conditioning in wild-type mice, and the general method of combining physical and structure-based screening may lead to the discovery of selective ligands for other GPCRs.
Xi-Ping Huang, Joel Karpiak, Wesley K. Kroeze et al. | | Ubiquitous time variability of integrated stellar populations
The number of long-period variable stars in a stellar population is directly related to their lifetime, which is difficult to predict from first principles; here a time-dependent stellar population model is constructed that includes the effects of long-period variable stars, and is applied to the galaxy M87.
Charlie Conroy, Pieter G. van Dokkum, Jieun Choi | 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.
David Turrà, Mennat El Ghalid, Federico Rossi et al. | Endoperoxide formation by an α-ketoglutarate-dependent mononuclear non-haem iron enzyme
The X-ray crystal structures of FtmOx1, the first known α-ketoglutarate-dependent mononuclear non-haem iron enzyme that can catalyse an endoperoxide formation reaction, are presented, along with further biochemical analyses which reveal the catalytic versatility of mononuclear non-haem iron enzymes, and help to unravel the mechanisms of endoperoxide biosyntheses.
Wupeng Yan, Heng Song, Fuhang Song et al. | Extremely metal-poor stars from the cosmic dawn in the bulge of the Milky Way
The first stars and their immediate successors should be found today in the central regions (bulges) of galaxies; old, metal-poor stars have now been found in the Milky Way bulge, including one star with an iron abundance about 10,000 times lower than that of the Sun without noticeable carbon enhancement, making it possibly the oldest known star in the Galaxy.
L. M. Howes, A. R. Casey, M. Asplund et al. | Type-II Weyl semimetals
A new type of topological semimetal is described, which contains so-called type-II Weyl fermions and has very different properties to standard Weyl semimetals, owing to the existence of an open Fermi surface rather than a point-like one in the vicinity of Weyl points; WTe2 is predicted to be one such semimetal.
Alexey A. Soluyanov, Dominik Gresch, Zhijun Wang et al. | Extra adsorption and adsorbate superlattice formation in metal-organic frameworks
Metal-organic frameworks have a porous structure that has useful applications in gas adsorption; here, small-angle X-ray scattering is used to visualize the process of adsorption as gas pressure increases, revealing that adsorbate molecules interact across pore walls in a way that allows extra adsorbate domains to be created in the framework and to form superlattices, before the adsorbate settles down into a more uniform distribution.
Hae Sung Cho, Hexiang Deng, Keiichi Miyasaka et al. | Single-molecule sequencing of the desiccation-tolerant grass Oropetium thomaeum OPEN
Oropetium thomaeum is a resurrection plant that can survive extreme water stress through desiccation to complete dryness, providing a model for drought tolerance; here, whole-genome sequencing and assembly of the Oropetium genome using single-molecule real-time sequencing is reported.
Robert VanBuren, Doug Bryant, Patrick P. Edger et al. | Foreign DNA capture during CRISPR–Cas adaptive immunity
The structure of the Cas1–Cas2 complex bound to a protospacer sequence illustrates how foreign DNA is captured and measured by bacterial proteins in preparation for integration into CRISPR loci.
James K. Nuñez, Lucas B. Harrington, Philip J. Kranzusch et al. | Sweet and bitter taste in the brain of awake behaving animals
Activation of the sweet and bitter cortical fields in awake mice evokes predetermined behavioural programs, independent of learning and experience, illustrating the hardwired and innate nature of the sense of taste.
Yueqing Peng, Sarah Gillis-Smith, Hao Jin et al. | Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer
Deletion of Twist or Snail, two key transcription factors that induce epithelial-to-mesenchymal transition in a mouse model of pancreatic ductal adenocarcinoma leads to an increase in cell proliferation, and a greater sensitivity to the chemotherapeutic agent gemcitabine, with no effect on invasion or metastasis.
Xiaofeng Zheng, Julienne L. Carstens, Jiha Kim et al. | Collisionless encounters and the origin of the lunar inclination
Gravitational interactions after the Moon-forming event suggest that the current lunar inclination is the result of collisionless encounters of planetesimals with the early Moon–Earth system.
Kaveh Pahlevan, Alessandro Morbidelli | Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging
Conventional clinical ultrasound imaging has, at best, sub-millimetre-scale resolution, but now a new ultrasound technique is demonstrated that is based on fast tracking of transient signals from a sub-wavelength contrast agent and has sufficiently high resolution to map the microvasculature deep into organs.
Claudia Errico, Juliette Pierre, Sophie Pezet et al. | Drosophila Ionotropic Receptor 25a mediates circadian clock resetting by temperature
A Drosophila chemosensory receptor, expressed in leg sensory neurons, is necessary for behavioural and molecular synchronization of the fly’s circadian clock to low-amplitude temperature cycles; this temperature-sensing pathway functions independently from the known temperature sensors of the fly’s antennae.
Chenghao Chen, Edgar Buhl, Min Xu et al. | 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.
Xing Zhang, Ke Ding, Xuekui Yu et al. | | | | |
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