Norepinephrine changes behavioral state via astroglial purinergic signaling.

Both neurons and glia communicate via diffusible neuromodulatory substances, but the substrates of computation in such neuromodulatory networks are unclear. During behavioral transitions in the larval zebrafish, the neuromodulator norepinephrine drives fast excitation and delayed inhibition of behavior and circuit activity. We find that the inhibitory arm of this feedforward motif is implemented by astroglial purinergic signaling. Neuromodulator imaging, behavioral pharmacology, and perturbations of neurons and astroglia reveal that norepinephrine triggers astroglial release of adenosine triphosphate, extracellular conversion into adenosine, and behavioral suppression through activation of hindbrain neuronal adenosine receptors. This work, along with a companion piece by Lefton and colleagues demonstrating an analogous pathway mediating the effect of norepinephrine on synaptic connectivity in mice, identifies a computational and behavioral role for an evolutionarily conserved astroglial purinergic signaling axis in norepinephrine-mediated behavioral and brain state transitions.

Full electrical manipulation of perpendicular exchange bias in ultrathin antiferromagnetic film with epitaxial strain.

Achieving effective manipulation of perpendicular exchange bias effect remains an intricate endeavor, yet it stands a significance for the evolution of ultra-high capacity and energy-efficient magnetic memory and logic devices. A persistent impediment to its practical applications is the reliance on external magnetic fields during the current-induced switching of exchange bias in perpendicularly magnetized structures. This study elucidates the achievement of a full electrical manipulation of the perpendicular exchange bias in the multilayers with an ultrathin antiferromagnetic layer. Owing to the anisotropic epitaxial strain in the 2-nm-thick IrMn3 layer, the considerable exchange bias effect is clearly achieved at room temperature. Concomitantly, a specific global uncompensated magnetization manifests in the IrMn3 layer, facilitating the switching of the irreversible portion of the uncompensated magnetization. Consequently, the perpendicular exchange bias can be manipulated by only applying pulsed current, notably independent of the presence of any external magnetic fields.

Imaging the extracellular matrix in live tissues and organisms with a glycan-binding fluorophore.

All multicellular systems produce and dynamically regulate extracellular matrices (ECM) that play important roles in both biochemical and mechanical signaling. Though the spatial arrangement of these extracellular assemblies is critical to their biological functions, visualization of ECM structure is challenging, in part because the biomolecules that compose the ECM are difficult to fluorescently label individually and collectively. Here, we present a cell-impermeable small molecule fluorophore, termed Rhobo6, that turns on and red shifts upon reversible binding to glycans. Given that most ECM components are densely glycosylated, the dye enables wash-free visualization of ECM, in systems ranging from in vitro substrates to in vivo mouse mammary tumors. Relative to existing techniques, Rhobo6 provides a broad substrate profile, superior tissue penetration, nonperturbative labeling, and negligible photobleaching. This work establishes a straightforward method for imaging the distribution of ECM in live tissues and organisms, lowering barriers for investigation of extracellular biology.

An inducible genetic tool to track and manipulate specific microglial states reveals their plasticity and roles in remyelination.

Recent single-cell RNA sequencing studies have revealed distinct microglial states in development and disease. These include proliferative-region-associated microglia (PAMs) in developing white matter and disease-associated microglia (DAMs) prevalent in various neurodegenerative conditions. PAMs and DAMs share a similar core gene signature. However, the extent of the dynamism and plasticity of these microglial states, as well as their functional significance, remains elusive, partly due to the lack of specific tools. Here, we generated an inducible Cre driver line, Clec7a-CreERT2, that targets PAMs and DAMs in the brain parenchyma. Utilizing this tool, we profiled labeled cells during development and in several disease models, uncovering convergence and context-dependent differences in PAM and DAM gene expression. Through long-term tracking, we demonstrated microglial state plasticity. Lastly, we specifically depleted DAMs in demyelination, revealing their roles in disease recovery. Together, we provide a versatile genetic tool to characterize microglial states in CNS development and disease.

Fast, Accurate, and Versatile Data Analysis Platform for the Quantification of Molecular Spatiotemporal Signals.

Optical recording of intricate molecular dynamics is becoming an indispensable technique for biological studies, accelerated by the development of new or improved biosensors and microscopy technology. This creates major computational challenges to extract and quantify biologically meaningful spatiotemporal patterns embedded within complex and rich data sources, many of which cannot be captured with existing methods. Here, we introduce Activity Quantification and Analysis (AQuA2), a fast, accurate, and versatile data analysis platform built upon advanced machine learning techniques. It decomposes complex live imaging-based datasets into elementary signaling events, allowing accurate and unbiased quantification of molecular activities and identification of consensus functional units. We demonstrate applications across a wide range of biosensors, cell types, organs, animal models, and imaging modalities. As exemplar findings, we show how AQuA2 identified drug-dependent interactions between neurons and astroglia, and distinct sensorimotor signal propagation patterns in the mouse spinal cord.

Direct and Inverse Spin Splitting Effects in Altermagnetic RuO2.

Recently, the altermagnetic materials with spin splitting effect (SSE), have drawn significant attention due to their potential to the flexible control of the spin polarization by the Néel vector. Here, the direct and inverse altermagnetic SSE (ASSE) in the (101)-oriented RuO2 film with the tilted Néel vector are reported. First, the spin torque along the x-, y-, and z-axis is detected from the spin torque-induced ferromagnetic resonance (ST-FMR), and the z-spin torque emerges when the electric current is along the [010] direction, showing the anisotropic spin splitting of RuO2. Further, the current-induced modulation of damping is used to quantify the damping-like torque efficiency (ξDL) in RuO2/Py, and an anisotropic ξDL is obtained and maximized for the current along the [010] direction, which increases with the reduction of the temperature, indicating the present of ASSE. Next, by way of spin pumping measurement, the inverse altermagnetic spin splitting effect (IASSE) is studied, which also shows a crystal direction-dependent anisotropic behavior and temperature-dependent behavior. This work gives a comprehensive study of the direct and inverse ASSE effects in the altermagnetic RuO2, inspiring future altermagnetic materials and devices with flexible control of spin polarization.

Probability-Distribution-Configurable True Random Number Generators Based on Spin-Orbit Torque Magnetic Tunnel Junctions.

The incorporation of randomness into stochastic computing can provide ample opportunities for applications such as simulated annealing, non-polynomial hard problem solving, and Bayesian neuron networks. In these cases, a considerable number of random numbers with an accurate and configurable probability distribution function (PDF) are indispensable. Preferably, these random numbers are provided at the hardware level to improve speed, efficiency, and parallelism. In this paper, how spin-orbit torque magnetic tunnel junctions (SOT-MTJs) with high barriers are suitable candidates for the desired true random number generators is demonstrated. Not only do these SOT-MTJs perform excellently in speed and endurance, but their randomness can also be conveniently and precisely controlled by a writing voltage, which makes them a well-performed Bernoulli bit. By utilizing these SOT-MTJ-based Bernoulli bits, any PDF, including Gaussian, uniform, exponential, Chi-square, and even arbitrarily defined distributions can be realized. These PDF-configurable true random number generators can then promise to advance the development of stochastic computing and broaden the applications of the SOT-MTJs.

The impact of intermittent hypoxemia on type 1 retinopathy of prematurity in preterm infants.

BACKGROUND: Intermittent hypoxemia (IH) may influence retinopathy of prematurity (ROP) development in preterm infants, however, previous studies had mixed results. This study tests the hypothesis that increased IH is associated with Type 1 ROP; a stage beyond which treatment is indicated. METHODS: IH was quantified by continuously monitoring oxygen saturation (SpO2) using high-resolution pulse oximeters during the first 10 weeks of life. Statistical analyses assessed the relationship and predictive ability of weekly and cumulative IH for Type 1 ROP development. RESULTS: Most analyses showed no association between IH and Type 1 ROP adjusting for gestational age (GA) and birth weight (BW). However, cumulative IH of longer duration during weeks 5-10, 6-10, and 7-10 were significantly associated with Type 1 ROP adjusting for GA and BW, e.g., the adjusted odds ratio of Type 1 ROP was 2.01 (p = 0.03) for every 3.8 seconds increase in IH duration from week 6-10. IH did not provide statistically significant added predictive ability above GA and BW. CONCLUSIONS: For most analyses there was no significant association between IH and Type 1 ROP adjusting for GA and BW. However, infants with longer IH duration during the second month of life had higher risk for Type 1 ROP. IMPACT: The relationship and predictive ability of intermittent hypoxemia (IH) on retinopathy of prematurity (ROP) is controversial. This study shows no significant association between IH events and Type 1 ROP after adjusting for gestational age (GA) and birth weight (BW), except for cumulative IH of longer duration in the second month of life. In this cohort, IH does not provide a statistically significant improvement in ROP prediction over GA and BW. This study is the first to assess the cumulative impact of IH measures on Type 1 ROP. Interventions for reducing IH duration during critical postnatal periods may improve ROP outcomes.

Conservation of neuron-astrocyte coordinated activity among sensory processing centers of the developing brain.

Afferent neurons in developing sensory organs exhibit a prolonged period of burst firing prior to the onset of sensory experience. This intrinsically generated activity propagates from the periphery through central processing centers to promote the survival and physiological maturation of neurons and refine their synaptic connectivity. Recent studies in the auditory system indicate that these bursts of action potentials also trigger metabotropic glutamate receptor-mediated calcium increases within astrocytes that are spatially and temporally correlated with neuronal events; however, it is not known if this phenomenon occurs in other sensory modalities. Here we show using in vivo simultaneous imaging of neuronal and astrocyte calcium activity in awake mouse pups that waves of retinal ganglion cell activity induce spatially and temporally correlated waves of astrocyte activity in the superior colliculus that depend on metabotropic glutamate receptors mGluR5 and mGluR3. Astrocyte calcium transients reliably occurred with each neuronal wave, but peaked more than one second after neuronal events. Despite differences in the temporal features of spontaneous activity in auditory and visual processing regions, individual astrocytes exhibited similar overall calcium activity patterns, providing a conserved mechanism to synchronize neuronal and astrocyte maturation within discrete sensory domains.

Restricted Boltzmann Machines Implemented by Spin-Orbit Torque Magnetic Tunnel Junctions.

Artificial intelligence has surged forward with the advent of generative models, which rely heavily on stochastic computing architectures enhanced by true random number generators with adjustable sampling probabilities. In this study, we develop spin-orbit torque magnetic tunnel junctions (SOT-MTJs), investigating their sigmoid-style switching probability as a function of the driving voltage. This feature proves to be ideally suited for stochastic computing algorithms such as the restricted Boltzmann machines (RBM) prevalent in pretraining processes. We exploit SOT-MTJs as both stochastic samplers and network nodes for RBMs, enabling the implementation of RBM-based neural networks to achieve recognition tasks for both handwritten and spoken digits. Moreover, we further harness the weights derived from the preceding image and speech training processes to facilitate cross-modal learning from speech to image generation. Our results clearly demonstrate that these SOT-MTJs are promising candidates for the development of hardware accelerators tailored for Boltzmann neural networks and other stochastic computing architectures.

Data science and its future in large neuroscience collaborations.

The rise of large scientific collaborations in neuroscience requires systematic, scalable, and reliable data management. How this is best done in practice remains an open question. To address this, we conducted a data science survey among currently active U19 grants, funded through the NIH's BRAIN Initiative. The survey was answered by both data science liaisons and Principal Investigators, speaking for ~500 researchers across 21 nation-wide collaborations. We describe the tools, technologies, and methods currently in use, and identify several shortcomings of current data science practice. Building on this survey, we develop plans and propose policies to improve data collection, use, publication, reuse and training in the neuroscience community.

Electrical-Controllable Antiferromagnet-Based Tunnel Junction.

An electrical-controllable antiferromagnet tunnel junction is a key goal in spintronics, holding immense promise for ultradense and ultrastable antiferromagnetic memory with high processing speed for modern information technology. Here, we have advanced toward this goal by achieving an electrical-controllable antiferromagnet-based tunnel junction of Pt/Co/Pt/Co/IrMn/MgO/Pt. The exchange coupling between antiferromagnetic IrMn and Co/Pt perpendicular magnetic multilayers results in the formation of an interfacial exchange bias and exchange spring in IrMn. Encoding information states "0" and "1" is realized through the exchange spring in IrMn, which can be electrically written by spin-orbit torque switching with high cyclability and electrically read by antiferromagnetic tunneling anisotropic magnetoresistance. Combining spin-orbit torque switching of both exchange spring and exchange bias, a 16 Boolean logic operation is successfully demonstrated. With both memory and logic functionalities integrated into our electrically controllable antiferromagnetic-based tunnel junction, we chart the course toward high-performance antiferromagnetic logic-in-memory.

Wearable fiber-free optical sensor for continuous monitoring of neonatal cerebral blood flow and oxygenation.

BACKGROUND: Unstable cerebral hemodynamics places preterm infants at high risk of brain injury. We adapted an innovative, fiber-free, wearable diffuse speckle contrast flow-oximetry (DSCFO) device for continuous monitoring of both cerebral blood flow (CBF) and oxygenation in neonatal piglets and preterm infants. METHODS: DSCFO uses two small laser diodes as focused-point and a tiny CMOS camera as a high-density two-dimensional detector to detect spontaneous spatial fluctuation of diffuse laser speckles for CBF measurement, and light intensity attenuations for cerebral oxygenation measurement. The DSCFO was first validated against the established diffuse correlation spectroscopy (DCS) in neonatal piglets and then utilized for continuous CBF and oxygenation monitoring in preterm infants during intermittent hypoxemia (IH) events. RESULTS: Significant correlations between the DSCFO and DCS measurements of CBF variations in neonatal piglets were observed. IH events induced fluctuations in CBF, cerebral oxygenation, and peripheral cardiorespiratory vitals in preterm infants. However, no consistent correlation patterns were observed among peripheral and cerebral monitoring parameters. CONCLUSIONS: This pilot study demonstrated the feasibility of DSCFO technology to serve as a low-cost wearable sensor for continuous monitoring of multiple cerebral hemodynamic parameters. The results suggested the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations. IMPACT: The innovative DSCFO technology may serve as a low-cost wearable sensor for continuous bedside monitoring of multiple cerebral hemodynamic parameters in neonatal intensive care units. Concurrent DSCFO and DCS measurements of CBF variations in neonatal piglet models generated consistent results. No consistent correlation patterns were observed among peripheral and cerebral monitoring parameters in preterm neonates, suggesting the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations during IH events. Integrating and correlating multiple cerebral functional parameters with clinical outcomes may identify biomarkers for prediction and management of IH associated brain injury.

Ultrastrong to nearly deep-strong magnon-magnon coupling with a high degree of freedom in synthetic antiferromagnets.

Ultrastrong and deep-strong coupling are two coupling regimes rich in intriguing physical phenomena. Recently, hybrid magnonic systems have emerged as promising candidates for exploring these regimes, owing to their unique advantages in quantum engineering. However, because of the relatively weak coupling between magnons and other quasiparticles, ultrastrong coupling is predominantly realized at cryogenic temperatures, while deep-strong coupling remains to be explored. In our work, we achieve both theoretical and experimental realization of room-temperature ultrastrong magnon-magnon coupling in synthetic antiferromagnets with intrinsic asymmetry of magnetic anisotropy. Unlike most ultrastrong coupling systems, where the counter-rotating coupling strength g2 is strictly equal to the co-rotating coupling strength g1, our systems allow for highly tunable g1 and g2. This high degree of freedom also enables the realization of normalized g1 or g2 larger than 0.5. Particularly, our experimental findings reveal that the maximum observed g1 is nearly identical to the bare frequency, with g1/ω0 = 0.963, indicating a close realization of deep-strong coupling within our hybrid magnonic systems. Our results highlight synthetic antiferromagnets as platforms for exploring unconventional ultrastrong and even deep-strong coupling regimes, facilitating the further exploration of quantum phenomena.

Creation of Room-Temperature Sub-100 nm Antiferromagnetic Skyrmions in an Antiferromagnet IrMn through Interfacial Exchange Coupling.

Antiferromagnetic (AFM) skyrmions are magnetic vortices composed of antiparallell-aligned neighboring spins. In stark contrast to conventional skyrmions based on ferromagnetic order, AFM skyrmions have vanished stray fields, higher response frequencies, and rectified translational motion driven by an external force. Therefore, AFM skyrmions promise highly efficient spintronics devices with high bit mobility and density. Nevertheless, the experimental realization of intrinsic AFM skyrmions remains elusive. Here, we show that AFM skyrmions can be nucleated via interfacial exchange coupling at the surface of a room-temperature AFM material, IrMn, exploiting the particular response from uncompensated moments to the thermal annealing and imprinting effects. Further systematic magnetic characterizations validate the existence of such an AFM order at the IrMn/CoFeB interfaces. Such AFM skyrmions have a typical size of 100 nm, which presents pronounced robustness against field and temperature. Our work opens new pathways for magnetic topological devices based on AFM skyrmions.

CAM3.0: determining cell type composition and expression from bulk tissues with fully unsupervised deconvolution.

MOTIVATION: Complex tissues are dynamic ecosystems consisting of molecularly distinct yet interacting cell types. Computational deconvolution aims to dissect bulk tissue data into cell type compositions and cell-specific expressions. With few exceptions, most existing deconvolution tools exploit supervised approaches requiring various types of references that may be unreliable or even unavailable for specific tissue microenvironments. RESULTS: We previously developed a fully unsupervised deconvolution method-Convex Analysis of Mixtures (CAM), that enables estimation of cell type composition and expression from bulk tissues. We now introduce CAM3.0 tool that improves this framework with three new and highly efficient algorithms, namely, radius-fixed clustering to identify reliable markers, linear programming to detect an initial scatter simplex, and a smart floating search for the optimum latent variable model. The comparative experimental results obtained from both realistic simulations and case studies show that the CAM3.0 tool can help biologists more accurately identify known or novel cell markers, determine cell proportions, and estimate cell-specific expressions, complementing the existing tools particularly when study- or datatype-specific references are unreliable or unavailable. AVAILABILITY AND IMPLEMENTATION: The open-source R Scripts of CAM3.0 is freely available at https://github.com/ChiungTingWu/CAM3/(https://github.com/Bioconductor/Contributions/issues/3205). A user's guide and a vignette are provided.

A Strategy for Enhancing Perpendicular Magnetic Anisotropy in Yttrium Iron Garnet Films.

In future information storage and processing, magnonics is one of the most promising candidates to replace traditional microelectronics. Yttrium iron garnet (YIG) films with perpendicular magnetic anisotropy (PMA) have aroused widespread interest in magnonics. Obtaining strong PMA in a thick YIG film with a small lattice mismatch (η) has been fascinating but challenging. Here, a novel strategy is proposed to reduce the required minimum strain value for producing PMA and increase the maximum thickness for maintaining PMA in YIG films by slight oxygen deficiency. Strong PMA is achieved in the YIG film with an η of only 0.4% and a film thickness up to 60 nm, representing the strongest PMA for such a small η reported so far. Combining transmission electron microscopy analyses, magnetic measurements, and a theoretical model, it is demonstrated that the enhancement of PMA physically originates from the reduction of saturation magnetization and the increase of magnetostriction coefficient induced by oxygen deficiency. The Gilbert damping values of the 60-nm-thick YIG films with PMA are on the order of 10-4 . This strategy improves the flexibility for the practical applications of YIG-based magnonic devices and provides promising insights for the theoretical understanding and the experimental enhancement of PMA in garnet films.

A Wearable Fluorescence Imaging Device for Intraoperative Identification of Human Brain Tumors.

Malignant glioma (MG) is the most common type of primary malignant brain tumors. Surgical resection of MG remains the cornerstone of therapy and the extent of resection correlates with patient survival. A limiting factor for resection, however, is the difficulty in differentiating the tumor from normal tissue during surgery. Fluorescence imaging is an emerging technique for real-time intraoperative visualization of MGs and their boundaries. However, most clinical grade neurosurgical operative microscopes with fluorescence imaging ability are hampered by low adoption rates due to high cost, limited portability, limited operation flexibility, and lack of skilled professionals with technical knowledge. To overcome the limitations, we innovatively integrated miniaturized light sources, flippable filters, and a recording camera to the surgical eye loupes to generate a wearable fluorescence eye loupe (FLoupe) device for intraoperative imaging of fluorescent MGs. Two FLoupe prototypes were constructed for imaging of Fluorescein and 5-aminolevulinic acid (5-ALA), respectively. The wearable FLoupe devices were tested on tumor-simulating phantoms and patients with MGs. Comparable results were observed against the standard neurosurgical operative microscope (PENTERO® 900) with fluorescence kits. The affordable and wearable FLoupe devices enable visualization of both color and fluorescence images with the same quality as the large and expensive stationary operative microscopes. The wearable FLoupe device allows for a greater range of movement, less obstruction, and faster/easier operation. Thus, it reduces surgery time and is more easily adapted to the surgical environment than unwieldy neurosurgical operative microscopes. Clinical and Translational Impact Statement-The affordable and wearable fluorescence imaging device developed in this study enables neurosurgeons to observe brain tumors with the same clarity and greater flexibility compared to bulky and costly operative microscopes.

Exceptional Hole-Selective Properties of Ta2O5 Films via Sn4+ Doping for High Performance Silicon Heterojunction Solar Cells.

Carrier-selective passivating contacts using transition metal oxides (TMOs) have attracted great attention for crystalline silicon (c-Si) heterojunction solar cells recently. Among them, tantalum oxide (Ta2O5) exhibits outstanding advantages, such as a wide bandgap, good surface passivation, and a small conduction band offset with c-Si, which is typically used as an electron-selective contact layer. Interestingly, it is first demonstrated that solution-processed Ta2O5 films exhibit a high hole selectivity, which blocks electrons and promotes hole transport simultaneously. Through the ozone pre-treatment of Ta2O5/p-Si interface and optimization of the film thickness (≈9 nm), the interfacial recombination is suppressed and the contact resistivity is reduced from 178.0 to 29.3 mΩ cm2. Moreover, the Sn4+ doping increases both the work function and oxygen vacancies of the film, contributing to the improved hole-selective contact performance. As a result, the photoelectric conversion efficiencies of Ta2O5/p-Si heterojunction solar cells are significantly improved from 14.84% to 18.47%, with a high thermal stability up to 300 °C. The work has provided a feasible strategy to explore new features of TMOs for carrier-selective contact applications, that is, bipolar carrier transport properties.