| | Neuroinflammation: Surprises from the sanitary engineers
In mammals, microglial cells of the central nervous system are responsible for the normal clearance of dead brain cells. TAM-receptor proteins have now been found to mediate this function. | Immunology: Organelle stress triggers inflammation
The intracellular NOD1 and NOD2 receptors have been found to activate innate inflammation when a condition known as endoplasmic reticulum stress is induced by bacterial infection. | Structural biology: Antidepressants at work
Structures of the serotonin transporter protein SERT in complex with two different antidepressants shed light on how these drugs act, and point to possible targets for future drug development. | Nuclear physics: Four neutrons together momentarily
A system of four neutrons known as the tetraneutron is a hypothetical state in nuclear physics. The report of evidence for the fleeting existence of this state has implications for research into neutron stars. | X-ray structures and mechanism of the human serotonin transporter
X-ray crystal structures of the human serotonin transporter (SERT) bound to the antidepressants (S)-citalopram or paroxetine show that the antidepressants lock the protein in an outward-open conformation, and directly block serotonin from entering its binding site; the structures define the mechanism of antidepressant action in SERT and pave the way for future drug design. | Modulation of tissue repair by regeneration enhancer elements
An injury-dependent enhancer element is identified that activates gene expression in regenerating zebrafish tissues and can be engineered into DNA constructs that increase tissue regenerative capacity; the element is also active in injured mouse tissue. | A neuronal circuit for colour vision based on rod–cone opponency
Colour vision is thought to rely on the comparison of signals from cone cells in the retina, this paper identifies a class of mouse retinal ganglion cells (J-RGC) that integrates an OFF signal from ultraviolet-sensitive cones with an ON signal from green-sensitive rods, producing a colour-opponent channel that may enable animals to detect urine territory marks; the underlying circuit may also explain why humans experience a blue shift in night-time vision. | Ritual human sacrifice promoted and sustained the evolution of stratified societies
Phylogenetic methods were applied to a cross-cultural database of traditional Austronesian societies to test the link between ritual human sacrifice and the origins of social hierarchy—the presence of sacrifice in a society stabilized social stratification and promoted inherited class systems. | Direct observation of dynamic shear jamming in dense suspensions
Dense suspensions of hard granular particles can transform from liquid-like to solid-like when perturbed; a state diagram is mapped out that reveals how this transformation can occur via dynamic jamming at sufficiently large shear stress while leaving the particle density unchanged. | Post-invasion demography of prehistoric humans in South America
South America was the last habitable continent to be colonized by humans; using a database of 1,147 archaeological sites and 5,464 radiocarbon dates spanning 14,000 to 2,000 years ago reveals two phases of the population history of the continent—a rapid expansion through the continent at low population sizes for over 8,000 years and then a second phase of sedentary lifestyle and exponential population growth starting around 5,000 years ago. | The Parkfield tremors reveal slow and fast ruptures on the same asperity
A tremor source on the San Andreas Fault produced an unusual sequence of low-frequency earthquakes until it was disrupted by the 2004 Parkfield earthquake; the peculiar recurrence pattern has now been modelled, showing that such slip behaviour occurs when the tremor asperity size is close to the critical nucleation size of earthquakes. | A 17-billion-solar-mass black hole in a group galaxy with a diffuse core
The galaxy NGC 1600 is found to contain an enormous black hole of 17 billion solar masses—the first black hole of such a size to be found in an environment outside the richest clusters of galaxies. | Crystal structure of the human σ1 receptor
The X-ray crystal structures of the human σ1 receptor bound to two different ligands are reported, revealing the overall architecture, oligomerization state, and molecular basis for ligand recognition by this protein. | sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance
Aged fibroblasts release a Wnt antagonist, sFRP2, which drives a signalling cascade in melanoma cells, leading to increased metastasis and reduced effectiveness of targeted therapy. | Reductive carboxylation supports redox homeostasis during anchorage-independent growth
Malignant cells are able to survive and grow in detached conditions, despite the associated increase in reactive oxygen species; here a novel metabolic pathway used by cancer cells as they adapt to anchorage-independent growth is described. | The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression
A study of pancreatic ductal adenocarcinoma shows that cancer cell proliferation is associated with increased expression of proteins that control programmed necrotic cell death and suppress the adaptive immune system. | A pressure-amplifying framework material with negative gas adsorption transitions
For adsorption processes, gas uptake usually increases with increasing pressure; however, here the phenomenon of negative gas adsorption is demonstrated in a metal–organic framework, which undergoes a sudden hysteretic structural deformation and pore contraction, releasing guest molecules. | TAM receptors regulate multiple features of microglial physiology
Microglial phagocytosis is required for neurogenic niche maintenance and response to injury; the TAM kinases Mer and Axl are expressed by microglia in the adult CNS, and mediate the clearance of apoptotic cells from the niche. | Ubiquitination independent of E1 and E2 enzymes by bacterial effectors
An unprecedented mechanism of ubiquitination that is independent of E1 and E2 enzymes, instead relying on activation of ubiquitin by ADP-ribosylation, and which is mediated by members of the SidE effector family encoded by the bacterial pathogen Legionella pneumophila, establishes that ubiquitination can be carried out by a single enzyme. | | Corrigendum: Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer | | | | 
EPIK™ miRNA Panel and Select Assays use miRNA-specific primers at both the RT and qPCR steps, in combination with SensiSMART™ mix and SYBR® Green, to deliver improved sensitivity, specificity and speed to the detection of miRNAs. | | | | | | | | | | | Climate-smart soils
The potential of soils to mitigate greenhouse gas emissions has not been exploited; here we discuss and recommend research and technology developments to implement mitigation practices.
Keith Paustian, Johannes Lehmann, Stephen Ogle et al. | | Thalamic reticular impairment underlies attention deficit in Ptchd1Y/− mice
Increased activity of dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens of rats during a ‘decision’ period reflects a ‘loss’ outcome of the previous decision, and predicts a subsequent safe choice; by artificially increasing the activity of D2R neurons during the decision period, risk-seeking rats could be converted to risk-avoiding rats.
Michael F. Wells, Ralf D. Wimmer, L. Ian Schmitt et al. | Candidalysin is a fungal peptide toxin critical for mucosal infection
This study identifies a cytolytic peptide toxin in the opportunistic human fungal pathogen Candida albicans—the peptide is both a crucial virulence factor that permeabilizes the host cell plasma membrane and a key signal that triggers a host danger response pathway.
David L. Moyes, Duncan Wilson, Jonathan P. Richardson et al. | | Structural basis of cohesin cleavage by separase
The crystal structures of the protease domain of separase are reported, showing how separase recognizes cohesin, and how phosphorylation of the cleavage site enhances separase activity.
Zhonghui Lin, Xuelian Luo, Hongtao Yu | Late Quaternary climate change shapes island biodiversity
Relatively rapid changes in island area, isolation and connectivity observed since the Last Glacial Maximum have had measurable effects on present-day biodiversity, with formerly larger and less well connected islands having a greater number of endemic species.
Patrick Weigelt, Manuel Jonas Steinbauer, Juliano Sarmento Cabral et al. | Cerebral cavernous malformations arise from endothelial gain of MEKK3–KLF2/4 signalling
Gain of MEKK3 signalling is shown to cause cerebral cavernous malformations (CCMs) via activation of the target genes Klf2 and Klf4; endothelial-specific loss of MEKK3, KLF2 or KLF4 prevents lesion formation and lethality in a mouse CCM model.
Zinan Zhou, Alan T. Tang, Weng-Yew Wong et al. | Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase
Thalidomide and its derivative lenalidomide bind the CRL4CRBN E3 ubiquitin ligase and target protein substrates for degradation; structural and functional data determined here show that casein kinase 1α and the lymphoid transcription factor Ikaros, the efficacy targets of lenalidomide in two different blood cancers, interact with the CRBN–lenalidomide interface through a β-hairpin destruction motif.
Georg Petzold, Eric S. Fischer, Nicolas H. Thomä | Recent near-Earth supernovae probed by global deposition of interstellar radioactive 60Fe
Analysis of deep-ocean archives reveals that a few per cent of fresh 60Fe has been captured in interstellar dust and deposited in Earth’s crust, indicating that many supernova events occurred over the past ten million years within a distance of up to 100 parsecs from Earth.
A. Wallner, J. Feige, N. Kinoshita et al. | The locations of recent supernovae near the Sun from modelling 60Fe transport
60Fe in deep-ocean crusts indicates that two supernovae exploded in the solar neighbourhood, reheating the superbubble that harbours our Solar System; calculations of the trajectories and masses of the supernova progenitors gives their explosion times and sites, 90–100 parsecs away, with masses around nine times the solar mass, at 2.3 and 1.5 million years ago, respectively.
D. Breitschwerdt, J. Feige, M. M. Schulreich et al. | Coherent feedback control of a single qubit in diamond
A feedback-control algorithm implemented using a solid-state spin qubit system associated with the nitrogen vacancy centre in diamond is demonstrated; the algorithm uses coherent feedback to overcome the limitations of measurement-based feedback and protects the qubit against intrinsic dephasing noise, making it stable for milliseconds.
Masashi Hirose, Paola Cappellaro | Nineteen-step total synthesis of (+)-phorbol
Enantiospecific total synthesis of (+)-phorbol in only 19 steps from the abundant monoterpene (+)-3-carene is demonstrated using a two-phase terpene synthesis strategy.
Shuhei Kawamura, Hang Chu, Jakob Felding et al. | A specific area of olfactory cortex involved in stress hormone responses to predator odours
Exposure to predator scents triggers an instinctive fear response in mice, including a surge in blood levels of stress hormones; here, the amygdalo-piriform transition area is identified as provoking these hormonal responses.
Kunio Kondoh, Zhonghua Lu, Xiaolan Ye et al. | Derivation and differentiation of haploid human embryonic stem cells
Haploid human embryonic stem cells have been derived from haploid oocytes, the cells maintain a normal haploid karyotype as pluripotent cells and, unexpectedly, as differentiated cells—loss-of-function genetic screens previously performed with haploid embryonic stem cells in mice can now be performed in humans.
Ido Sagi, Gloryn Chia, Tamar Golan-Lev et al. | Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1
Uncoupling protein 1 (UCP1)-dependent thermogenesis in brown adipose tissue is supported by a burst of mitochondrial reactive oxygen species upon cold exposure.
Edward T. Chouchani, Lawrence Kazak, Mark P. Jedrychowski et al. | Quantum hydrogen-bond symmetrization in the superconducting hydrogen sulfide system
Ab initio calculations are used to determine the contribution of quantum fluctuations to the crystal structure of the high-pressure superconducting phase of H3S and D3S; the quantum nature of the proton is found to fundamentally change the superconducting phase diagram of H3S.
Ion Errea, Matteo Calandra, Chris J. Pickard et al. | Continuous directional water transport on the peristome surface of Nepenthes alata
Insects are captured by the carnivorous plant Nepenthes alata when they ‘aquaplane’ on the wet rim, or ‘peristome’, of the plant’s pitcher organ; here it is shown that unidirectional water flow is crucial to the complete wetting of the peristome, and that the underlying mechanism involves multiscale structural features.
Huawei Chen, Pengfei Zhang, Liwen Zhang et al. | Northern Hemisphere hydroclimate variability over the past twelve centuries
A very large set of proxy data is used to reconstruct Northern Hemisphere hydroclimate variability over the past twelve centuries, to benchmark climate model simulations of hydroclimate; the twentieth-century intensification of hydroclimate extremes seen in the model simulations is not supported by the proxy reconstruction.
Fredrik Charpentier Ljungqvist, Paul J. Krusic, Hanna S. Sundqvist et al. | Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia
Lypd8 protein derived from intestinal epithelial cells binds to flagellated bacteria to reduce their motility, which limits the entry of Gram-negative bacteria into the inner colonic mucus and prevents invasion of colonic epithelia.
Ryu Okumura, Takashi Kurakawa, Takashi Nakano et al. | | | | |
