Individualized temporal patterns drive human sleep spindle timing.

Sleep spindles are cortical electrical oscillations considered critical for memory consolidation and sleep stability. The timing and pattern of sleep spindles are likely to be important in driving synaptic plasticity during sleep as well as preventing disruption of sleep by sensory and internal stimuli. However, the relative importance of factors such as sleep depth, cortical up/down-state, and temporal clustering in governing sleep spindle dynamics remains poorly understood.

Role of the stratosphere in the global mercury cycle.

Mercury (Hg) is a global pollutant with substantial risks to human and ecosystem health. By upward transport in tropical regions, mercury enters into the stratosphere, but the contribution of the stratosphere to global mercury dispersion and deposition remains unknown. We find that between 5 and 50% (passing through the 400-kelvin isentropic surface and tropopause, respectively) of the mercury mass deposited on Earth's surface is chemically processed in the lower stratosphere.

Thickness-dependent polaron crossover in tellurene.

Polarons, quasiparticles from electron-phonon coupling, are crucial for material properties including high-temperature superconductivity and colossal magnetoresistance. However, scarce studies have investigated polaron formation in low-dimensional materials with phonon polarity and electronic structure transitions. In this work, we studied polarons of tellurene, composed of chiral Te chains.

No Bridge between Us: EXAFS and Computations Confirm Two Distant Iron Ions Comprise the Active Site of Alkane Monooxygenase (AlkB).

Alkane monooxygenase (AlkB) is the dominant enzyme that catalyzes the oxidation of liquid alkanes in the environment. Two recent structural models derived from cryo-electron microscopy (cryo-EM) reveal an unusual active site: a histidine-rich center that binds two iron ions without a bridging ligand. To ensure that potential photoreduction and radiation damage are not responsible for the absence of a bridging ligand in the cryo-EM structures, spectroscopic methods are needed.

Bio-Orchestration of Cellular Organization and Human-Preferred Sensory Texture in Cultured Meat.

For cultured meat to effectively replace traditional meat, it is essential to develop scaffolds that replicate key attributes of real meat, such as taste, nutrition, flavor, and texture. However, one of the significant challenges in replicating meat characteristics with scaffolds lies in the considerable gap between the stiffness preferred by cells and the textural properties desired by humans. To address this issue, we focused on the microscale environment conducive to cell growth and the macro-scale properties favored by humans.

Hydrogel-Gated MXene-Graphene Field-Effect Transistor for Selective Detection and Screening of SARS-CoV-2 and Bacteria.

Field-effect transistor (FET) biosensors have significantly attracted interest across various disciplines because of their high sensitivity, time-saving, and label-free characteristics. However, it remains a grand challenge to interface the FET biosensor with complex liquid media. Unlike standard liquid electrolytes containing purified protein content, directly exposing FET biosensors to complex biological fluids introduces significant sensing noise, which is caused by the abundance of nonspecific proteins, viruses, and bacteria that adsorb to the biosensor surfaces.

Domain Adversarial Convolutional Neural Network Improves the Accuracy and Generalizability of Wearable Sleep Assessment Technology.

Wearable accelerometers are widely used as an ecologically valid and scalable solution for long-term at-home sleep monitoring in both clinical research and care. In this study, we applied a deep learning domain adversarial convolutional neural network (DACNN) model to this task and demonstrated that this new model outperformed existing sleep algorithms in classifying sleep-wake and estimating sleep outcomes based on wrist-worn accelerometry. This model generalized well to another dataset based on different wearable devices and activity counts, achieving an accuracy of 80.

Development of a PET Probe Targeting Bromodomain and Extra-Terminal Proteins for In Vitro and In Vivo Visualization.

Bromodomain and extra-terminal (BET) proteins are critical regulators of gene transcription, as they recognize acetylated lysine residues. The BD1 bromodomain of BRD4, a member of the BET family, has emerged as a promising therapeutic target for various diseases. This study aimed to develop and evaluate a novel C-11 labeled PET radiotracer, [C]YL10, for imaging the BD1 bromodomain of BRD4 in vivo.

Advances in 2D Molybdenum Disulfide Transistors for Flexible and Wearable Electronics.

As the trajectory of developing advanced electronics is shifting towards wearable electronics, various methods for implementing flexible and bendable devices capable of conforming to curvilinear surfaces have been widely investigated. In particular, achieving high-performance and stable flexible transistors remains a significant technical challenge, as transistors are fundamental components of electronics, playing a key role in overall performance. Among the wide range of candidates for flexible transistors, two-dimensional (2D) molybdenum disulfide (MoS)-based transistors have emerged as potential solutions to address these challenges.

Indocyanine Blue (ICB) as a Functional Alternative to Indocyanine Green (ICG) for Enhanced 700 nm NIR Imaging.

Despite significant advancements in bioimaging technology, only a limited number of fluorophores are currently approved for clinical applications. Indocyanine green (ICG) is the first FDA-approved near-infrared (NIR) fluorophore and has significantly advanced clinical interventions over the past three decades. However, its single-channel imaging at 800 nm emission is often insufficient for capturing comprehensive diagnostic information during surgery.

A Practical Clinical Approach to Navigate Pulmonary Embolism Management: A Primer and Narrative Review of the Evolving Landscape.

Advances in imaging, pharmacological, and procedural technologies have rapidly expanded the care of pulmonary embolism. Earlier, more accurate identification and quantification has enhanced risk stratification across the spectrum of the disease process, with a number of clinical tools available to prognosticate outcomes and guide treatment. Direct oral anticoagulants have enabled a consistent and more convenient long-term therapeutic option, with a greater shift toward outpatient treatment for a select group of low-risk patients.

Opening the AI Black Box: Distilling Machine-Learned Algorithms into Code.

Can we turn AI black boxes into code? Although this mission sounds extremely challenging, we show that it is not entirely impossible by presenting a proof-of-concept method, MIPS, that can synthesize programs based on the automated mechanistic interpretability of neural networks trained to perform the desired task, auto-distilling the learned algorithm into Python code. We test MIPS on a benchmark of 62 algorithmic tasks that can be learned by an RNN and find it highly complementary to GPT-4: MIPS solves 32 of them, including 13 that are not solved by GPT-4 (which also solves 30). MIPS uses an integer autoencoder to convert the RNN into a finite state machine, then applies Boolean or integer symbolic regression to capture the learned algorithm.

Age- and Sex-Based Developmental Biomarkers in Eye Movements.

Background: Eye movement research serves as a critical tool for assessing brain function, diagnosing neurological and psychiatric disorders, and understanding cognition and behavior. Sex differences have largely been under reported or ignored in neurological research. However, eye movement features provide biomarkers that are useful for disease classification with superior accuracy and robustness compared to previous classifiers for neurological diseases.

Exploring the Dynamics of Canine-Assisted Interactions: A Wearable Approach to Understanding Interspecies Well-Being.

Canine-assisted interactions (CAIs) have been explored to offer therapeutic benefits to human participants in various contexts, from addressing cancer-related fatigue to treating post-traumatic stress disorder. Despite their widespread adoption, there are still unresolved questions regarding the outcomes for both humans and animals involved in these interactions. Previous attempts to address these questions have suffered from core methodological weaknesses, especially due to absence of tools for an efficient objective evaluation and lack of focus on the canine perspective.

Distribution of potentially toxic elements in sediments of the municipal river channel (Balu), Dhaka, Bangladesh: Ecological and health risks assessment.

The concern of potential toxic elements (PTEs) contamination in the river ecosystem is growing due to anthropological activity. The contents of seven PTEs in sediments from the Balu River channel were analyzed using atomic absorption spectroscopy (AAS) and an environmental risk model. Several PTEs were found in the sediment at high levels, including zinc (Zn), copper (Cu), arsenic (As), lead (Pb), cadmium (Cd), nickel (Ni), and mercury (Hg), that might pose a risk to human and ecological health.

Prognostic significance of serum complement activation, neutrophil extracellular traps and extracellular DNA in newly diagnosed epithelial ovarian cancer.

Purpose: We observed that the tumor microenvironment (TME) in metastatic epithelial ovarian cancer (EOC) and in other solid tumors can reprogram normal neutrophils to acquire a complement-dependent suppressor phenotype characterized by inhibition of stimulated T cell activation. This study aims to evaluate whether serum markers of neutrophil activation and complement at diagnosis of EOC would be associated with clinical outcomes.

Experimental Design: We conducted a two-center prospective study of patients with newly diagnosed EOC (N = 188).

Evaluating the Reliability of a Microperimetry-Based Method for Assessing Visual Function in the Junctional Zone of Geographic Atrophy Lesions.

Purpose: To assess the repeatability of a microperimetry methodology for quantifying visual function changes in the junctional zone of eyes with geographic atrophy (GA) in the clinical trial context.

Methods: A post hoc analysis of the OAKS phase III trial was conducted, which enrolled patients with GA secondary to age-related macular degeneration. Microperimetry using a standard 10-2 fovea centered grid was performed at baseline and follow-up visits.

Differentiating BOLD and non-BOLD signals in fMRI time series using cross-cortical depth delay patterns.

Over the past two decades, rapid advancements in magnetic resonance technology have significantly enhanced the imaging resolution of functional Magnetic Resonance Imaging (fMRI), far surpassing its initial capabilities. Beyond mapping brain functional architecture at unprecedented scales, high-spatial-resolution acquisitions have also inspired and enabled several novel analytical strategies that can potentially improve the sensitivity and neuronal specificity of fMRI. With small voxels, one can sample from different levels of the vascular hierarchy within the cerebral cortex and resolve the temporal progression of hemodynamic changes from parenchymal to pial vessels.

Universality of representation in biological and artificial neural networks.

Many artificial neural networks (ANNs) trained with ecologically plausible objectives on naturalistic data align with behavior and neural representations in biological systems. Here, we show that this alignment is a consequence of convergence onto the same representations by high-performing ANNs and by brains. We developed a method to identify stimuli that systematically vary the degree of inter-model representation agreement.

An Expanded Registry of Candidate cis-Regulatory Elements for Studying Transcriptional Regulation.

Mammalian genomes contain millions of regulatory elements that control the complex patterns of gene expression. Previously, The ENCODE consortium mapped biochemical signals across many cell types and tissues and integrated these data to develop a Registry of 0.9 million human and 300 thousand mouse candidate cis-Regulatory Elements (cCREs) annotated with potential functions.

BRAF and ErbB inhibitors directly activate GCN2 in an off-target manner to limit cancer cell proliferation.

Targeted kinase inhibitors are well known for their promiscuity and off-target effects. Herein, we define an off-target effect in which several clinical BRAF inhibitors, including the widely used dabrafenib and encorafenib, interact directly with GCN2 to activate the Integrated Stress Response and ATF4. Blocking this off-target effect by co-drugging with a GCN2 inhibitor in A375 melanoma cells causes enhancement rather than suppression of cancer cell outgrowth, suggesting that the off-target activation of GCN2 is detrimental to these cells.

UTX Epigenetically Imposes a Cytolytic Effector Program in Autoreactive Stem-like CD8+ T cell Progenitors.

Type 1 Diabetes Mellitus (T1D) is an autoimmune disease caused by unremitting immune attack on pancreas insulin-producing beta cells. Persistence of the autoimmune response is mediated by TCF1+ Ly108+ progenitor CD8+ T (T) cells, a stem-like population that gives rise to exhausted effectors with limited cytolytic function in chronic virus infection and cancer. What paradoxically drives T conversion to highly cytolytic effectors in T1D, however, remains unclear.

Glycan analysis probes inspired by human lectins for investigating host-microbe crosstalk.

Human lectins are critical carbohydrate-binding proteins that recognize diverse glycoconjugates from microorganisms and can play a key role in host-microbe interactions. Despite their importance in immune recognition and pathogen binding, the specific glycan ligands and functions of many human lectins remain poorly understood. Using previous proof-of-concept studies on selected lectins as the foundation for this work, we present ten additional glycan analysis probes (GAPs) from a diverse set of human soluble lectins, offering robust tools to investigate glycan-mediated interactions.

The PRMT5-splicing axis is a critical oncogenic vulnerability that regulates detained intron splicing.

Protein arginine methyltransferase 5 (PRMT5) is a promising cancer target, yet it's unclear which PRMT5 roles underlie this vulnerability. Here, we establish that PRMT5 inhibition induces a special class of unspliced introns, called detained introns (DIs). To interrogate the impact of DIs, we depleted CLNS1A, a PRMT5 cofactor that specifically enables Sm protein methylation.