Refilling the coral reef glass ()

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News at a glance ()

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A fiery finish to Cassini's long run at Saturn ()

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A legacy of discovery ()

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Russia heightens defenses against climate change ()

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Why is the flu vaccine so mediocre? ()

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Researchers parse ecosystems fueled by chemistry, not light ()

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How ApoE4 endangers brains ()

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Death watch for climate probe ()

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Embryo edit makes human 'knockout ()

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China's childhood experiment ()

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Toward pesticidovigilance ()

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RNA localization feeds translation ()

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The social origins of persistence ()

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Advances in organ transplant from pigs ()

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Angular momentum can slow down photoemission ()

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New angle on cosmic rays ()

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Sociotechnical transitions for deep decarbonization ()

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The legacy of the Spanish flu ()

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Sleight of hand ()

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Editorial expression of concern ()

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Saving the saola from extinction ()

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Addressing scientific integrity scientifically ()

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North Korea ban blocks humanitarians ()

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Poison frogs resist their own chemical defense ()

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Neandertal growth patterns ()

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An early call for plate tectonics ()

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Helping people and their businesses grow ()

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Taking the PERVs out of pigs ()

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How the sucker comes to grip ()

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Photoemission with a twist ()

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Editing FAK to be more metastatic ()

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Human-derived neurons provide the answers ()

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Phase separation and cellular organization ()

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Universal scaling for big quakes ()

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Multitalented enhancers ()

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Cutting out circular RNAs ()

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Location, location, location ()

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High-energy particles are extragalactic ()

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If at first you don't succeed, try again ()

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A better system for pesticide regulation ()

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Tackling T cells in GVHD ()

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Killing viral helicases ()

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Carbon capture from the industrial sector ()

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Impulsivity and procrastination ()

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Electrochemically driven box-weaving ()

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Two of a kind ()

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Neuroinflammation abetted by ILCs ()

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MicroRNA processing (phase) separated ()

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Too many bad seeds ()

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Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinsons disease ()
Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson’s disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic neurons derived from patients with idiopathic and familial PD. We identified a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation and ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction, and α-synuclein accumulation. This toxic cascade was observed in human, but not in mouse, PD neurons at least in part because of species-specific differences in dopamine metabolism. Increasing dopamine synthesis or α-synuclein amounts in mouse midbrain neurons recapitulated pathological phenotypes observed in human neurons. Thus, dopamine oxidation represents an important link between mitochondrial and lysosomal dysfunction in PD pathogenesis.
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Interacting amino acid replacements allow poison frogs to evolve epibatidine resistance ()
Animals that wield toxins face self-intoxication. Poison frogs have a diverse arsenal of defensive alkaloids that target the nervous system. Among them is epibatidine, a nicotinic acetylcholine receptor (nAChR) agonist that is lethal at microgram doses. Epibatidine shares a highly conserved binding site with acetylcholine, making it difficult to evolve resistance yet maintain nAChR function. Electrophysiological assays of human and frog nAChR revealed that one amino acid replacement, which evolved three times in poison frogs, decreased epibatidine sensitivity but at a cost of acetylcholine sensitivity. However, receptor functionality was rescued by additional amino acid replacements that differed among poison frog lineages. Our results demonstrate how resistance to agonist toxins can evolve and that such genetic changes propel organisms toward an adaptive peak of chemical defense.
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Observation of a large-scale anisotropy in the arrival directions of cosmic rays above 8 x 1018 eV ()
Cosmic rays are atomic nuclei arriving from outer space that reach the highest energies observed in nature. Clues to their origin come from studying the distribution of their arrival directions. Using 3 x 104 cosmic rays with energies above 8 x 1018 electron volts, recorded with the Pierre Auger Observatory from a total exposure of 76,800 km2 sr year, we determined the existence of anisotropy in arrival directions. The anisotropy, detected at more than a 5.2 level of significance, can be described by a dipole with an amplitude of 6.5–0.9+1.3 percent toward right ascension αd = 100 ± 10 degrees and declination d = –24–13+12 degrees. That direction indicates an extragalactic origin for these ultrahigh-energy particles.
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Titanium isotopic evidence for felsic crust and plate tectonics 3.5 billion years ago ()
Earth exhibits a dichotomy in elevation and chemical composition between the continents and ocean floor. Reconstructing when this dichotomy arose is important for understanding when plate tectonics started and how the supply of nutrients to the oceans changed through time. We measured the titanium isotopic composition of shales to constrain the chemical composition of the continental crust exposed to weathering and found that shales of all ages have a uniform isotopic composition. This can only be explained if the emerged crust was predominantly felsic (silica-rich) since 3.5 billion years ago, requiring an early initiation of plate tectonics. We also observed a change in the abundance of biologically important nutrients phosphorus and nickel across the Archean-Proterozoic boundary, which might have helped trigger the rise in atmospheric oxygen.
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Angular momentum-induced delays in solid-state photoemission enhanced by intra-atomic interactions ()
Attosecond time-resolved photoemission spectroscopy reveals that photoemission from solids is not yet fully understood. The relative emission delays between four photoemission channels measured for the van der Waals crystal tungsten diselenide (WSe2) can only be explained by accounting for both propagation and intra-atomic delays. The intra-atomic delay depends on the angular momentum of the initial localized state and is determined by intra-atomic interactions. For the studied case of WSe2, the photoemission events are time ordered with rising initial-state angular momentum. Including intra-atomic electron-electron interaction and angular momentum of the initial localized state yields excellent agreement between theory and experiment. This has required a revision of existing models for solid-state photoemission, and thus, attosecond time-resolved photoemission from solids provides important benchmarks for improved future photoemission models.
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The hidden simplicity of subduction megathrust earthquakes ()
The largest observed earthquakes occur on subduction interfaces and frequently cause widespread damage and loss of life. Understanding the rupture behavior of megathrust events is crucial for earthquake rupture physics, as well as for earthquake early-warning systems. However, the large variability in behavior between individual events seemingly defies a description with a simple unifying model. Here we use three source time function (STF) data sets for subduction zone earthquakes, with moment magnitude Mw ≥ 7, and show that such large ruptures share a typical universal behavior. The median STF is scalable between events with different sizes, grows linearly, and is nearly triangular. The deviations from the median behavior are multiplicative and Gaussian—that is, they are proportionally larger for larger events. Our observations suggest that earthquake magnitudes cannot be predicted from the characteristics of rupture onsets.
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The growth pattern of Neandertals, reconstructed from a juvenile skeleton from El Sidron (Spain) ()
Ontogenetic studies help us understand the processes of evolutionary change. Previous studies on Neandertals have focused mainly on dental development and inferred an accelerated pace of general growth. We report on a juvenile partial skeleton (El Sidrón J1) preserving cranio-dental and postcranial remains. We used dental histology to estimate the age at death to be 7.7 years. Maturation of most elements fell within the expected range of modern humans at this age. The exceptions were the atlas and mid-thoracic vertebrae, which remained at the 5- to 6-year stage of development. Furthermore, endocranial features suggest that brain growth was not yet completed. The vertebral maturation pattern and extended brain growth most likely reflect Neandertal physiology and ontogenetic energy constraints rather than any fundamental difference in the overall pace of growth in this extinct human.
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Teaching personal initiative beats traditional training in boosting small business in West Africa ()
Standard business training programs aim to boost the incomes of the millions of self-employed business owners in developing countries by teaching basic financial and marketing practices, yet the impacts of such programs are mixed. We tested whether a psychology-based personal initiative training approach, which teaches a proactive mindset and focuses on entrepreneurial behaviors, could have more success. A randomized controlled trial in Togo assigned microenterprise owners to a control group (n = 500), a leading business training program (n = 500), or a personal initiative training program (n = 500). Four follow-up surveys tracked outcomes for firms over 2 years and showed that personal initiative training increased firm profits by 30%, compared with a statistically insignificant 11% for traditional training. The training is cost-effective, paying for itself within 1 year.
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Infants make more attempts to achieve a goal when they see adults persist ()
Persistence, above and beyond IQ, is associated with long-term academic outcomes. To look at the effect of adult models on infants’ persistence, we conducted an experiment in which 15-month-olds were assigned to one of three conditions: an Effort condition in which they saw an adult try repeatedly, using various methods, to achieve each of two different goals; a No Effort condition in which the adult achieved the goals effortlessly; or a Baseline condition. Infants were then given a difficult, novel task. Across an initial study and two preregistered experiments (N = 262), infants in the Effort condition made more attempts to achieve the goal than did infants in the other conditions. Pedagogical cues modulated the effect. The results suggest that adult models causally affect infants’ persistence and that infants can generalize the value of persistence to novel tasks.
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PAF1 regulation of promoter-proximal pause release via enhancer activation ()
Gene expression in metazoans is regulated by RNA polymerase II (Pol II) promoter-proximal pausing and its release. Previously, we showed that Pol II–associated factor 1 (PAF1) modulates the release of paused Pol II into productive elongation. Here, we found that PAF1 occupies transcriptional enhancers and restrains hyperactivation of a subset of these enhancers. Enhancer activation as the result of PAF1 loss releases Pol II from paused promoters of nearby PAF1 target genes. Knockout of PAF1-regulated enhancers attenuates the release of paused Pol II on PAF1 target genes without major interference in the establishment of pausing at their cognate promoters. Thus, a subset of enhancers can primarily modulate gene expression by controlling the release of paused Pol II in a PAF1-dependent manner.
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Global mRNA polarization regulates translation efficiency in the intestinal epithelium ()
Asymmetric messenger RNA (mRNA) localization facilitates efficient translation in cells such as neurons and fibroblasts. However, the extent and importance of mRNA polarization in epithelial tissues are unclear. Here, we used single-molecule transcript imaging and subcellular transcriptomics to uncover global apical-basal intracellular polarization of mRNA in the mouse intestinal epithelium. The localization of mRNAs did not generally overlap protein localization. Instead, ribosomes were more abundant on the apical sides, and apical transcripts were consequently more efficiently translated. Refeeding of fasted mice elicited a basal-to-apical shift in polarization of mRNAs encoding ribosomal proteins, which was associated with a specific boost in their translation. This led to increased protein production, required for efficient nutrient absorption. These findings reveal a posttranscriptional regulatory mechanism involving dynamic polarization of mRNA and polarized translation.
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Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 ()
Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. In addition to the concerns about pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (PERVs) has impeded the clinical application of this approach. We previously demonstrated the feasibility of inactivating PERV activity in an immortalized pig cell line. We now confirm that PERVs infect human cells, and we observe the horizontal transfer of PERVs among human cells. Using CRISPR-Cas9, we inactivated all of the PERVs in a porcine primary cell line and generated PERV-inactivated pigs via somatic cell nuclear transfer. Our study highlights the value of PERV inactivation to prevent cross-species viral transmission and demonstrates the successful production of PERV-inactivated animals to address the safety concern in clinical xenotransplantation.
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Gordon Research Conferences ()

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New Products ()

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Sunshine outside the ivory tower ()

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Liquid phase condensation in cell physiology and disease ()
Phase transitions are ubiquitous in nonliving matter, and recent discoveries have shown that they also play a key role within living cells. Intracellular liquid-liquid phase separation is thought to drive the formation of condensed liquid-like droplets of protein, RNA, and other biomolecules, which form in the absence of a delimiting membrane. Recent studies have elucidated many aspects of the molecular interactions underlying the formation of these remarkable and ubiquitous droplets and the way in which such interactions dictate their material properties, composition, and phase behavior. Here, we review these exciting developments and highlight key remaining challenges, particularly the ability of liquid condensates to both facilitate and respond to biological function and how their metastability may underlie devastating protein aggregation diseases.
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Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function ()
Hundreds of circular RNAs (circRNAs) are highly abundant in the mammalian brain, often with conserved expression. Here we show that the circRNA Cdr1as is massively bound by the microRNAs (miRNAs) miR-7 and miR-671 in human and mouse brains. When the Cdr1as locus was removed from the mouse genome, knockout animals displayed impaired sensorimotor gating—a deficit in the ability to filter out unnecessary information—which is associated with neuropsychiatric disorders. Electrophysiological recordings revealed dysfunctional synaptic transmission. Expression of miR-7 and miR-671 was specifically and posttranscriptionally misregulated in all brain regions analyzed. Expression of immediate early genes such as Fos, a direct miR-7 target, was enhanced in Cdr1as-deficient brains, providing a possible molecular link to the behavioral phenotype. Our data indicate an in vivo loss-of-function circRNA phenotype and suggest that interactions between Cdr1as and miRNAs are important for normal brain function.
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Erratum for the Review "Quantum simulations with ultracold atoms in optical lattices" by C. Gross and I. Bloch ()

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