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Coupling of Slow Oscillations in the Prefrontal and Motor Cortex Predicts Onset of Spindle Trains and Persistent Memory Reactivations

Sleep is known to drive the consolidation of motor memories. During nonrapid eye movement (NREM) sleep, the close temporal proximity between slow oscillations (SOs) and spindles ("nesting" of SO-spindles) is known to be essential for consolidation, likely because it is closely associated with the reactivation of awake task activity. Interestingly, recent work has found that spindles can occur in temporal clusters or "trains." However, it remains unclear how spindle trains are related to the nesting phenomenon. Here, we hypothesized that spindle trains are more likely when SOs co-occur in the prefrontal and motor cortex. We conducted simultaneous neural recordings in the medial prefrontal cortex (mPFC) and primary motor cortex (M1) of male rats training on the reach-to-grasp motor task. We found that intracortically recorded M1 spindles are organized into distinct temporal clusters. Notably, the occurrence of temporally precise SOs between mPFC and M1 was a strong predictor of spindle trains. Moreover, reactivation of awake task patterns is much more persistent during spindle trains in comparison with that during isolated spindles. Together, our work suggests that the precise coupling of SOs across mPFC and M1 may be a potential driver of spindle trains and persistent reactivation of motor memory during NREM sleep.




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Distinct Neuron Types Contribute to Hybrid Auditory Spatial Coding

Neural decoding is a tool for understanding how activities from a population of neurons inside the brain relate to the outside world and for engineering applications such as brain–machine interfaces. However, neural decoding studies mainly focused on different decoding algorithms rather than different neuron types which could use different coding strategies. In this study, we used two-photon calcium imaging to assess three auditory spatial decoders (space map, opponent channel, and population pattern) in excitatory and inhibitory neurons in the dorsal inferior colliculus of male and female mice. Our findings revealed a clustering of excitatory neurons that prefer similar interaural level difference (ILD), the primary spatial cues in mice, while inhibitory neurons showed random local ILD organization. We found that inhibitory neurons displayed lower decoding variability under the opponent channel decoder, while excitatory neurons achieved higher decoding accuracy under the space map and population pattern decoders. Further analysis revealed that the inhibitory neurons’ preference for ILD off the midline and the excitatory neurons’ heterogeneous ILD tuning account for their decoding differences. Additionally, we discovered a sharper ILD tuning in the inhibitory neurons. Our computational model, linking this to increased presynaptic inhibitory inputs, was corroborated using monaural and binaural stimuli. Overall, this study provides experimental and computational insight into how excitatory and inhibitory neurons uniquely contribute to the coding of sound locations.




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PDE4B Missense Variant Increases Susceptibility to Post-traumatic Stress Disorder-Relevant Phenotypes in Mice

Large-scale genome-wide association studies (GWASs) have associated intronic variants in PDE4B, encoding cAMP-specific phosphodiesterase-4B (PDE4B), with increased risk for post-traumatic stress disorder (PTSD), as well as schizophrenia and substance use disorders that are often comorbid with it. However, the pathophysiological mechanisms of genetic risk involving PDE4B are poorly understood. To examine the effects of PDE4B variation on phenotypes with translational relevance to psychiatric disorders, we focused on PDE4B missense variant M220T, which is present in the human genome as rare coding variant rs775201287. When expressed in HEK-293 cells, PDE4B1-M220T exhibited an attenuated response to a forskolin-elicited increase in the intracellular cAMP concentration. In behavioral tests, homozygous Pde4bM220T male mice with a C57BL/6JJcl background exhibited increased reactivity to novel environments, startle hyperreactivity, prepulse inhibition deficits, altered cued fear conditioning, and enhanced spatial memory, accompanied by an increase in cAMP signaling pathway-regulated expression of BDNF in the hippocampus. In response to a traumatic event (10 tone–shock pairings), neuronal activity was decreased in the cortex but enhanced in the amygdala and hippocampus of Pde4bM220T mice. At 24 h post-trauma, Pde4bM220T mice exhibited increased startle hyperreactivity and decreased plasma corticosterone levels, similar to phenotypes exhibited by PTSD patients. Trauma-exposed Pde4bM220T mice also exhibited a slower decay in freezing at 15 and 30 d post-trauma, demonstrating enhanced persistence of traumatic memories, similar to that exhibited by PTSD patients. These findings provide substantive mouse model evidence linking PDE4B variation to PTSD-relevant phenotypes and thus highlight how genetic variation of PDE4B may contribute to PTSD risk.




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Transcriptomic Correlates of State Modulation in GABAergic Interneurons: A Cross-Species Analysis

GABAergic inhibitory interneurons comprise many subtypes that differ in their molecular, anatomical, and functional properties. In mouse visual cortex, they also differ in their modulation with an animal’s behavioral state, and this state modulation can be predicted from the first principal component (PC) of the gene expression matrix. Here, we ask whether this link between transcriptome and state-dependent processing generalizes across species. To this end, we analysed seven single-cell and single-nucleus RNA sequencing datasets from mouse, human, songbird, and turtle forebrains. Despite homology at the level of cell types, we found clear differences between transcriptomic PCs, with greater dissimilarities between evolutionarily distant species. These dissimilarities arise from two factors: divergence in gene expression within homologous cell types and divergence in cell-type abundance. We also compare the expression of cholinergic receptors, which are thought to causally link transcriptome and state modulation. Several cholinergic receptors predictive of state modulation in mouse interneurons are differentially expressed between species. Circuit modelling and mathematical analyses suggest conditions under which these expression differences could translate into functional differences.




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Retinal Input to Macaque Superior Colliculus Derives from Branching Axons Projecting to the Lateral Geniculate Nucleus

The superior colliculus receives a direct projection from retinal ganglion cells. In primates, it remains unknown if the same ganglion cells also supply the lateral geniculate nucleus. To address this issue, a double-label experiment was performed in two male macaques. The animals fixated a target while injection sites were scouted in the superior colliculus by recording and stimulating with a tetrode. Once suitable sites were identified, cholera toxin subunit B-Alexa Fluor 488 was injected via an adjacent micropipette. In a subsequent acute experiment, cholera toxin subunit B-Alexa Fluor 555 was injected into the lateral geniculate nucleus at matching retinotopic locations. After a brief survival period, ganglion cells were examined in retinal flatmounts. The percentage of double-labeled cells varied locally, depending on the relative efficiency of retrograde transport by each tracer and the precision of retinotopic overlap of injection sites in each target nucleus. In counting boxes with extensive overlap, 76–98% of ganglion cells projecting to the superior colliculus were double labeled. Cells projecting to the superior colliculus constituted 4.0–6.7% of the labeled ganglion cell population. In one particularly large zone, there were 5,746 cells labeled only by CTB-AF555, 561cells double labeled by CTB-AF555 and CTB-AF488, but no cell labeled only by CTB-AF488. These data indicate that retinal input to the macaque superior colliculus arises from a collateral axonal branch supplied by ~5% of the ganglion cells that project to the lateral geniculate nucleus. Surprisingly, there exist no ganglion cells that project exclusively to the SC.




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Cortically Disparate Visual Features Evoke Content-Independent Load Signals during Storage in Working Memory

It is well established that holding information in working memory (WM) elicits sustained stimulus-specific patterns of neural activity. Nevertheless, here we provide evidence for a distinct class of neural activity that tracks the number of individuated items in working memory, independent of the type of visual features stored. We present two EEG studies of young adults of both sexes that provide robust evidence for a signal tracking the number of individuated representations in working memory, regardless of the specific feature values stored. In Study 1, subjects maintained either colors or orientations across separate blocks in a single session. We found near-perfect generalization of the load signal between these two conditions, despite being able to simultaneously decode which feature had been voluntarily stored. In Study 2, participants attended to two features with very distinct cortical representations: color and motion coherence. We again found evidence for a neural load signal that robustly generalized across these distinct visual features, even though cortically disparate regions process color and motion coherence. Moreover, representational similarity analysis provided converging evidence for a content-independent load signal, while simultaneously showing that unique variance in EEG activity tracked the specific features that were stored. We posit that this load signal reflects a content-independent "pointer" operation that binds objects to the current context while parallel but distinct neural signals represent the features that are stored for each item in memory.




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The Effect of Congruent versus Incongruent Distractor Positioning on Electrophysiological Signals during Perceptual Decision-Making

Key event-related potentials (ERPs) of perceptual decision-making such as centroparietal positivity (CPP) elucidate how evidence is accumulated toward a given choice. Furthermore, this accumulation can be impacted by visual target selection signals such as the N2 contralateral (N2c). How these underlying neural mechanisms of perceptual decision-making are influenced by the spatial congruence of distractors relative to target stimuli remains unclear. Here, we used electroencephalography (EEG) in humans of both sexes to investigate the effect of distractor spatial congruency (same vs different hemifield relative to targets) on perceptual decision-making. We confirmed that responses for perceptual decisions were slower for spatially incongruent versus congruent distractors of high salience. Similarly, markers of target selection (N2c peak amplitude) and evidence accumulation (CPP slope) were found to be lower when distractors were spatially incongruent versus congruent. To evaluate the effects of congruency further, we applied drift diffusion modeling to participant responses, which showed that larger amplitudes of both ERPs were correlated with shorter nondecision times when considering the effect of congruency. The modeling also suggested that congruency's effect on behavior occurred prior to and during evidence accumulation when considering the effects of the N2c peak and CPP slope. These findings point to spatially incongruent distractors, relative to congruent distractors, influencing decisions as early as the initial sensory processing phase and then continuing to exert an effect as evidence is accumulated throughout the decision-making process. Overall, our findings highlight how key electrophysiological signals of perceptual decision-making are influenced by the spatial congruence of target and distractor.




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G-Protein Signaling in Alzheimer's Disease: Spatial Expression Validation of Semi-supervised Deep Learning-Based Computational Framework

Systemic study of pathogenic pathways and interrelationships underlying genes associated with Alzheimer's disease (AD) facilitates the identification of new targets for effective treatments. Recently available large-scale multiomics datasets provide opportunities to use computational approaches for such studies. Here, we devised a novel disease gene identification (digID) computational framework that consists of a semi-supervised deep learning classifier to predict AD-associated genes and a protein–protein interaction (PPI) network-based analysis to prioritize the importance of these predicted genes in AD. digID predicted 1,529 AD-associated genes and revealed potentially new AD molecular mechanisms and therapeutic targets including GNAI1 and GNB1, two G-protein subunits that regulate cell signaling, and KNG1, an upstream modulator of CDC42 small G-protein signaling and mediator of inflammation and candidate coregulator of amyloid precursor protein (APP). Analysis of mRNA expression validated their dysregulation in AD brains but further revealed the significant spatial patterns in different brain regions as well as among different subregions of the frontal cortex and hippocampi. Super-resolution STochastic Optical Reconstruction Microscopy (STORM) further demonstrated their subcellular colocalization and molecular interactions with APP in a transgenic mouse model of both sexes with AD-like mutations. These studies support the predictions made by digID while highlighting the importance of concurrent biological validation of computationally identified gene clusters as potential new AD therapeutic targets.




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Neural Representations of Concreteness and Concrete Concepts Are Specific to the Individual

Different people listening to the same story may converge upon a largely shared interpretation while still developing idiosyncratic experiences atop that shared foundation. What linguistic properties support this individualized experience of natural language? Here, we investigate how the "concrete–abstract" axis—the extent to which a word is grounded in sensory experience—relates to within- and across-subject variability in the neural representations of language. Leveraging a dataset of human participants of both sexes who each listened to four auditory stories while undergoing functional magnetic resonance imaging, we demonstrate that neural representations of "concreteness" are both reliable across stories and relatively unique to individuals, while neural representations of "abstractness" are variable both within individuals and across the population. Using natural language processing tools, we show that concrete words exhibit similar neural representations despite spanning larger distances within a high-dimensional semantic space, which potentially reflects an underlying representational signature of sensory experience—namely, imageability—shared by concrete words but absent from abstract words. Our findings situate the concrete–abstract axis as a core dimension that supports both shared and individualized representations of natural language.




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Pre- and Postsynaptic MEF2C Promotes Experience-Dependent, Input-Specific Development of Cortical Layer 4 to Layer 2/3 Excitatory Synapses and Regulates Activity-Dependent Expression of Synaptic Cell Adhesion Molecules

Experience- and activity-dependent transcription is a candidate mechanism to mediate development and refinement of specific cortical circuits. Here, we demonstrate that the activity-dependent transcription factor myocyte enhancer factor 2C (MEF2C) is required in both presynaptic layer (L) 4 and postsynaptic L2/3 mouse (male and female) somatosensory (S1) cortical neurons for development of this specific synaptic connection. While postsynaptic deletion of Mef2c weakens L4 synaptic inputs, it has no effect on inputs from local L2/3, contralateral S1, or the ipsilateral frontal/motor cortex. Similarly, homozygous or heterozygous deletion of Mef2c in presynaptic L4 neurons weakens L4 to L2/3 excitatory synaptic inputs by decreasing presynaptic release probability. Postsynaptic MEF2C is specifically required during an early postnatal, experience-dependent, period for L4 to L2/3 synapse function, and expression of transcriptionally active MEF2C (MEF2C-VP16) rescues weak L4 to L2/3 synaptic strength in sensory-deprived mice. Together, these results suggest that experience- and/or activity-dependent transcriptional activation of MEF2C promotes development of L4 to L2/3 synapses. Additionally, MEF2C regulates the expression of many pre- and postsynaptic genes in postnatal cortical neurons. Interestingly, MEF2C was necessary for activity-dependent expression of many presynaptic genes, including those that function in transsynaptic adhesion and neurotransmitter release. This work provides mechanistic insight into the experience-dependent development of specific cortical circuits.




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How Century-Old Paintings Reveal the Indigenous Roots and Natural History of New England Landscapes

Seven guest collaborators bring new eyes to a Smithsonian museum founder’s collection of American art




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How an Indigenous Weaver’s Mastery of Color Infuses Her Tapestries With a Life Force

The work of Diné artist DY Begay, now on view at the National Museum of the American Indian, blends tradition and modernity




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See What Happened When One Museum Asked Artists to Define ‘Home’

The Smithsonian Design Triennial presents 25 commissions that explore the physical and conceptual ideas of shelter and refuge




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Pope Francis to attend the Second International Conference on Nutrition (ICN2)

Pope Francis will add his voice to the fight against hunger and malnutrition by addressing the Second International [...]




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Morocco's first South-South Cooperation agreement to benefit Guinea and other countries in Africa

Building on previous efforts, the Kingdom of Morocco will offer technical assistance to the Republic of Guinea through a South-South Cooperation Tripartite Agreement signed today at FAO headquarters by FAO [...]




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FAO appoints Prince Laurent of Belgium Special Ambassador for Forests and the Environment

Prince Laurent of Belgium was today appointed FAO Special Ambassador for Forests and the Environment.

The announcement was made by FAO Director-General José Graziano da Silva at the Organization’s Committee on [...]




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South-South Cooperation

A recent side event during the Council last week promoted South-South Cooperation (SSC) as a cost-effective means to addressing food insecurity, showcased FAO’s role as a facilitator and voiced the [...]




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FAO urges Europe to support nutrition and sustainable farming

Milan - European governments must help combat [...]




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FAO Director-General appoints Jacques Diouf as FAO Special Envoy for the Sahel and the Horn of Africa

FAO Director-General José Graziano da Silva today appointed Jacques Diouf as Special Envoy for the Horn of Africa and the Sahel.

In his new role, the former Director-General Jacques Diouf will [...]




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Director General opens FAO Council meeting

FAO Director-General Graziano da Silva today opened the 150th session of the FAO Council, highlighting the successful conclusion of the Second International Conference on Nutrition (ICN2), held last month in [...]




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International Conference on South-South Cooperation praises FAO's leadership and facilitation role

Marrakesh, 15 December 2014 – African Ministers of Agriculture recognized the facilitating role of FAO “under the new strategic framework established with the leadership of the [...]




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FAO launches new South-South Cooperation Gateway: an information sharing platform

South-South Cooperation is the mutual sharing and exchange of development solutions - knowledge, experiences and good practices, policies, technology and resources - between and among countries in the global [...]




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FAO Permanent Representatives conclude field visit to Laos

Vientiane.- A delegation of seven Permanent Representatives to the Rome-based Food and Agriculture Organization of the U.N (FAO) concluded a week-long visit to Lao PDR, during which they held meetings [...]




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Turning performance around

Published by the United Kingdom’s Department for International Development (DFID), the latest Multilateral Development Review describes FAO as a [...]




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FAO tapped to lead a global dialogue to mainstream biodiversity in agriculture, forestry and fisheries

Cancun, Mexico. On [...]




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FAO Open Day

As part of the Open House Roma Initiative, FAO is joining over 200 sites around Rome and is opening its doors to the public on 6 and 7 May. This [...]




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FAO will support Colombia in making sure the new peace is kept

I am convinced that the only path to lasting peace in Colombia consists of dialogue, negotiation, cooperation, inclusion and fairness – which is also the high road to sustainable development [...]




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Launch of The State of Food Security and Nutrition in the World 2017 - Building resilience for peace and food security

The international community has committed to ending hunger and malnutrition by 2030. But can we overcome the obstacles that stand in the way of meeting this target?

The State [...]




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This World Food Day, Pope Francis addresses FAO and the international community

World Food Day is coming up this Monday, October 16. This year’s theme, Change the future of migration. Invest in food security and rural development, highlights FAO’s work in [...]




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FAO Open Day

After the success of the “FAO Open Day” last year, the second FAO OPEN DAY will take place on Saturday 12 and Sunday 13 May 2018, as part of the [...]




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Launch of a series of Activity Books for young people

The Food and Agriculture Organization of the United Nations (FAO) has the pleasure to inform the Permanent Representatives of the launch of a series of Activity Books for young people. [...]




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FAO Open Day

Visit FAO on 11 or 12 May to find out about FAO’s mandate and work, and its key role in supporting countries in their efforts to achieve Zero Hunger. This [...]




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FAO to host a Special Seminar on Food and Nutrition - 25 November

This special seminar calls us to take a new look at how to channel our knowledge, stimulate innovative thinking and guide our actions to expedite agri-food system transformation and achieve [...]




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FAO - Globally Important Agricultural Heritage Systems Programme call for experts

Rome - The FAO - Globally Important Agricultural Heritage Systems Programme opens the process of establishing a new Scientific Advisory Groupfor the 2021-2022 term.  The Programme is seeking for [...]





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ROME WATER DIALOGUE, a Special Event on the road to the UN 2023 Water Conference 29 November 2022, 09.00-16.15 (CET)

Water is one of the world´s most important resources. It is central to agriculture that accounts for 72 percent of global freshwater withdrawals, to other economic sectors and is essential [...]




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FAO in review: Building and deploying professional and practical expertise

Read the seriesFull Article



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Opening Ceremony of the International Year of Millets 2023

The Food and Agriculture Organization of the United Nations (FAO) would like to invite you to the opening ceremony of the International Year of Millets 2023

 




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FAO's GIAHS Programme seeks new experts for the Scientific Advisory Group

Rome - The Food and Agriculture Organization (FAO) is currently seeking applications from experts to join the Scientific Advisory Group (SAG) of its Globally Important Agricultural Heritage Systems [...]




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FAO Brief - Sudan, ARC33, and tackling plant pests

In this episode, FAO calls for more funding and resources for farmers in Sudan to prevent the escalation of the hunger crisis; FAO’s Director-General emphasized Africa’s potential for development at [...]




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New Technical Cooperation Programme Website

The PSS Technical Cooperation Programme (TCP) team is excited to announce the launch of its newly designed webpages. The webpage has a fresh look [...]




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Advancing sustainable inland fisheries and aquaculture in Europe: EIFAAC hosts 32nd Session and International Symposium

The European Inland Fisheries and Aquaculture Advisory Commission (EIFAAC) is dedicated to the sustainable development and responsible management of European inland fisheries and aquaculture. In line with the [...]




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Ask Smithsonian: Why Do We Have an Appendix?

The appendix may not be as useless as commonly thought.




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Pioneering Video Artist Peter Campus Presents His Version of the Star-Spangled Banner




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Stratford-upon-Avon Is a Magnet for Shakespeare Lovers

To soar over Stratford-upon-Avon in Warwickshire is to be transported back in time to the age of William Shakespeare, a man born in humble circumstances who would go on to become the most celebrated writer of all time.




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Denali Has One of the Deepest Canyons in the World

Ruth Glacier’s Great Gorge is quite simply one of the continent’s most awe-inspiring sights. At 2,000 feet and over ten miles long, it’s one of the deepest canyons in the world.




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What Happens When Galaxies Collide?

In about four billion years from now, the Milky Way and Andromeda galaxies will crash together Visualization: NASA, ESA, and F. Summers, STScI Simulation credit: NASA, ESA, G. Besla, Columbia University, and R. van der Marel, STScI




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SmartNews: Apps for Apes

Zookeepers at the National Zoo keep orangutans mentally stimulated with an innovative use of iPads




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This Bandit-Faced Dino Hid From Predators Using Multiple Types of Camouflage

Credit: David Marshall, University of Bristol




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The Invisible Enemy Wiping Out Entire Species of Frogs

To save a species from extinction, scientists scour the Panamanian jungle for the few remaining frogs. But will they be too late?