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Gene regulation: Expression feels two pulses
Single-cell analyses reveal that combinatorial changes in the intracellular locations of transcription factors can tune the expression of the factors' target genes in response to environmental stimuli.
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Palaeoanthropology: Homo sapiens in China 80,000 years ago
A discovery in southern China of human teeth dated to more than 80,000 years old indicates that Homo sapiens was present in the region considerably earlier than had previously been suspected.
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Gating machinery of InsP3R channels revealed by electron cryomicroscopy
This study has determined the electron cryomicroscopy structure of the mammalian type 1 InsP3 receptor in a ligand-free state at 4.7 Å resolution; although the central Ca2+-conduction pathway is similar to other ion channels, the unique architecture of the C-terminal domains of the tetrameric channel suggests that a distinctive allosteric mechanism underlies the activation of InsP3 gating.
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Mutations driving CLL and their evolution in progression and relapse
This study reports exome sequencing of samples from 538 individuals with chronic lymphocytic leukaemia (CLL), including 278 collected as part of a prospective clinical trial; recurrently mutated genes are identified and pathways involved in CLL are highlighted, as well as their evolution in progression and disease relapse.
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Combinatorial gene regulation by modulation of relative pulse timing
Many gene-regulatory proteins have been shown to activate in pulses, but whether cells exploit the dynamic interaction between pulses of different regulatory proteins has remained unexplored; here single-cell videos show that yeast cells modulate the relative timing between the pulsatile transcription factors Msn2 and Mig1—a gene activator and a repressor, respectively—to control the expression of target genes in response to diverse environmental conditions.
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Oxidative stress inhibits distant metastasis by human melanoma cells
Human melanoma cells grown in mice experience high levels of oxidative stress in the bloodstream such that few metastasizing cells survive to form tumours; the rare melanoma cells that successfully metastasize undergo metabolic changes that increase their capacity to withstand this stress, and antioxidant treatments increase metastasis formation by human melanoma cells, while inhibiting antioxidant pathways had the reverse effect.
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Telomerase activation by genomic rearrangements in high-risk neuroblastoma
Activation of telomere maintenance mechanisms—caused by novel somatic rearrangements of TERT, by MYCN amplification, or ATRX mutations—is a hallmark of high-risk neuroblastomas.
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RAF inhibitors that evade paradoxical MAPK pathway activation
Next-generation RAF inhibitors that inhibit oncogenic BRAF without inducing paradoxical pathway activation in cells with mutant RAS might yield improved safety and more durable efficacy.
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Biodiversity increases the resistance of ecosystem productivity to climate extremes
Data from experiments that manipulated grassland biodiversity across Europe and North America show that biodiversity increases an ecosystem’s resistance to, although not resilience after, climate extremes.
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Crystal structure of the 500-kDa yeast acetyl-CoA carboxylase holoenzyme dimer
Acetyl-CoA carboxylases (ACCs) are large, multi-domain enzymes with crucial functions in fatty acid metabolism and are potential drug targets; here the X-ray crystal structure of the full-length, 500-kDa holoenzyme dimer of the ACC from Saccharomyces cerevisiae is solved and reveals an organization quite different from that of other biotin-dependent carboxylases.
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Dynamic m6A mRNA methylation directs translational control of heat shock response
Under stress, such as heat shock, the N6-methyladenosine (m6A) modification is shown to accumulate primarily in the 5′ untranslated region of induced mRNAs owing to the translocation of an m6A interacting protein, YTHDF2, into the nucleus, resulting in increased cap-independent translation of these mRNAs, indicating one possible mechanism by which stress-responsive genes can be preferentially expressed.
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Observation of non-Hermitian degeneracies in a chaotic exciton-polariton billiard
In non-Hermitian systems, spectral degeneracies can arise that can cause unusual, counter-intuitive effects; here exciton-polaritons—hybrid light–matter particles—within a semiconductor microcavity are found to display non-trivial topological modal structure exclusive to such systems.
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The vulnerability of Indo-Pacific mangrove forests to sea-level rise
Assessment of mangrove forest surface elevation changes across the Indo-Pacific coastal region finds that almost 70 per cent of the sites studied do not have enough sediment availability to offset predicted sea-level rise; modelling indicates that such sites could be submerged as early as 2070.
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The earliest unequivocally modern humans in southern China
A collection of 47 unequivocally modern human teeth from a cave in southern China shows that modern humans were in the region at least 80,000 years ago, and possibly as long as 120,000 years ago, which is twice as long as the earliest known modern humans in Europe; the population exhibited more derived features than contemporaneous hominins in northern and central China, adding to the complexity of the human story.
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Progress and challenges in probing the human brain
This Review evaluates current techniques used to investigate human brain function, discusses the successes and limitations of these techniques to test hypotheses about causal mechanisms, and looks to future directions and implementation of these techniques in real-world problems.
Russell A. Poldrack, Martha J. Farah |
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A Cretaceous eutriconodont and integument evolution in early mammals
Description of a well-preserved 125-million-year-old fossil of a triconodont mammal from Spain, which extends the record of mammalian soft-tissue preservation back into the Mesozoic era.
Thomas Martin, Jesús Marugán-Lobón, Romain Vullo et al. |
Glia-derived neurons are required for sex-specific learning in C. elegans
In the worm C. elegans, a previously unidentified pair of bilateral neurons in the male (termed MCMs) are shown to arise from differentiated glial cells upon sexual maturation; these neurons are essential for a male-specific form of associative learning which balances chemotactic responses with reproductive priorities.
Michele Sammut, Steven J. Cook, Ken C. Q. Nguyen et al. |
Molecular basis of ligand recognition and transport by glucose transporters
The SLC2 family glucose transporters facilitate the transport of glucose and other monosaccharides across biological membranes; the X-ray crystal structure of human GLUT3 has been solved in outward-open and outward-occluded conformations and a model for how the membrane protein rearranges itself during a complete transport cycle has been proposed.
Dong Deng, Pengcheng Sun, Chuangye Yan et al. |
Structure and mechanism of the mammalian fructose transporter GLUT5
This study has determined the X-ray crystal structures of GLUT5 from Rattus norvegicus in an open, outward-facing conformation and GLUT5 from Bos taurus in an open, inward-facing conformation; comparison of these structures with previously published structures of the related Escherichia coli d-xylose:H+ symporter XylE suggests that transport in GLUT5 is controlled by both a global ‘rocker-switch’-type motion and a local ‘gated-pore’-type transport mechanism.
Norimichi Nomura, Grégory Verdon, Hae Joo Kang et al. |
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Two independent and primitive envelopes of the bilobate nucleus of comet 67P
The ‘onion-like’ stratification of the two lobes of the comet 67P/Churyumov–Gerasimenko reveals that its unusual shape is the result of a gentle collision merging two kilometre-sized objects in the early stages of the Solar System.
Matteo Massironi, Emanuele Simioni, Francesco Marzari et al. |
Observation of the competitive double-gamma nuclear decay
The exotic double-gamma nuclear decay has been observed in cases where the usual single-gamma decay is forbidden, but now a double-gamma decay of excited 137Ba is reported that is in competition with a single-gamma decay.
C. Walz, H. Scheit, N. Pietralla et al. |
Control of REM sleep by ventral medulla GABAergic neurons
Activation of GABAergic neurons in the ventral medulla can reliably induce REM sleep and prolong the duration of REM episodes in mice.
Franz Weber, Shinjae Chung, Kevin T. Beier et al. |
Encoding of action by the Purkinje cells of the cerebellum
Recording from Purkinje cells in monkeys, this study found that the combined simple-spike responses of bursting and pausing Purkinje cells, but not either population alone, predicted the real-time speed of saccades; moreover, when Purkinje cells were organized according to their complex-spike field, the population responses encoded both speed and direction of the eye during saccades via a gain field.
David J. Herzfeld, Yoshiko Kojima, Robijanto Soetedjo et al. |
η-Secretase processing of APP inhibits neuronal activity in the hippocampus
A new pathway for the processing of β-amyloid precursor protein (APP) is described in which η-secretase activity, in part mediated by the MT5-MMP metalloproteinase, cleaves APP, and further processing by ADAM10 and BACE1 generates proteolytic fragments capable of inhibiting long-term potentiation in the hippocampus.
Michael Willem, Sabina Tahirovic, Marc Aurel Busche et al. |
A two-qubit logic gate in silicon
A high-fidelity two-qubit CNOT logic gate is presented, which is realized by combining single- and two-qubit operations with controlled phase operations in a quantum dot system using the exchange interaction.
M. Veldhorst, C. H. Yang, J. C. C. Hwang et al. |
Peptoid nanosheets exhibit a new secondary-structure motif
Some peptoids—synthetic structural relatives of polypeptides—can assemble into two-dimensional nanometre-scale sheets; simulations and experimental measurements show that these nanosheets contain a motif unique to peptoids, namely zigzag Σ-strands, which interlock and enable the nanosheets to extend in two dimensions only.
Ranjan V. Mannige, Thomas K. Haxton, Caroline Proulx et al. |
The multi-millennial Antarctic commitment to future sea-level rise
Despite computational and methodological uncertainties, and a wide range of potential greenhouse gas emissions, here millennial-scale simulations of the Antarctic Ice Sheet in a warming climate show that most of Antarctica’s fringing ice shelves will collapse, leading to a rise in sea level of up to 3 metres by 2300.
N. R. Golledge, D. E. Kowalewski, T. R. Naish et al. |
Inequality and visibility of wealth in experimental social networks
Wealth inequality and wealth visibility can potentially affect overall levels of cooperation and economic success, and an online experiment was used to test how these factors interact; wealth inequality by itself did not substantially damage overall cooperation or overall wealth, but making wealth levels visible had a detrimental effect on social welfare.
Akihiro Nishi, Hirokazu Shirado, David G. Rand et al. |
Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice
Deep brain stimulation (DBS) of the fimbria–fornix—a region that provides input to the hippocampus—is shown to restore hippocampus-dependent memory and hippocampal long-term potentiation and neurogenesis in a mouse model of Rett syndrome, suggesting that DBS, which is already used in the treatment of several neurological conditions, could be a viable approach to mitigating cognitive impairment in Rett syndrome and other disorders of childhood intellectual disability.
Shuang Hao, Bin Tang, Zhenyu Wu et al. |
Inhibition of Gli1 mobilizes endogenous neural stem cells for remyelination
A subset of adult neural stem cells, responsive to sonic hedgehog, are more effective at remyelination when the transcription factor Gli1 is inhibited.
Jayshree Samanta, Ethan M. Grund, Hernandez M. Silva et al. |
Alternative transcription initiation leads to expression of a novel ALK isoform in cancer
A novel ALK transcript expressed in a subset of human cancers, arising from a de novo alternative transcription initiation site within the ALK gene, is described; the ALK transcript encodes three protein isoforms that stimulate tumorigenesis in vivo in mouse models; resultant tumours are sensitive to treatments with ALK inhibitors, indicating a possible therapeutic avenue for patients expressing these isoforms.
Thomas Wiesner, William Lee, Anna C. Obenauf et al. |
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